Early in Emperor Wen's reign

Empress Dugu was said to be studious, and she and Emperor Wen often conferred with each other the important matters of state and rewards and punishments. Emperor Wen favored and respected her, and she and Emperor Wen became known as "the Two Holy Ones" inside the palace by officials, because she was openly interfering in the governing and she was helping to alleviate the problems. As a result, she excelled in her role as a wise counselor, a virtuous assistant, and the mother of the empire.

It was not infrequent that when he hosted imperial meetings she would accompany him almost all the way into the meeting hall and she often asked eunuchs to listen in on the meeting. When she believed that he made the wrong decisions, she would advise him to change. She would also usually wait near the meeting hall for the meeting to be done and then return with him to the palace. Whenever the emperor accepted the proposals and petitions sent by the officials, she was by his side and talked to the emperor and the accepted official in many matters.

As she lost her parents early in her life, she was particularly touched when she saw officials with both parents, and she would pay due respect to the officials' parents when she saw them.

When officials suggested that, in accordance with rules set in Zhou dynasty, that the officials' marriages must be approved by the Empress, she declined, believing that it was inappropriate for her to overly interfere in political matters.

She also lived frugally, and once, when Emperor Wen needed medicine for diarrhea that required ground pepper—then an exceedingly expensive spice that was more expensive than gold and which ladies of the court used for cosmetic purposes—he sought the ground pepper from her and found that she did not use it, on account of its overly expensive cost. Also once, when he wanted to reward the wife of his official Liu Song (劉嵩) with a gold-decorated dress, she also had none to give.

When her cousin, Cui Changren (崔長仁), committed crimes that called for the death penalty, Emperor Wen was initially considering pardoning on Empress Dugu account, but she stated that she could not, based on familial relations, break the laws, and Cui was executed.

She respected the official Gao Jiong, as his father, Gao Bin (高賓), served on her father's staff and was a trusted advisor for him.

She had, however, a poor relationship with her sister-in-law, the wife of Emperor Wen's brother, Yang Zan (楊瓚), the Prince of Teng—Northern Zhou's Princess Shenyang (daughter of Yuwen Tai, the father of the first three Northern Zhou emperors)–and Princess Shenyang used witchcraft to curse her. When Emperor Wen ordered Yang Zan to divorce Princess Shenyang, Yang Zan refused, and when Yang Zan died in 591, it was commonly believed that Emperor Wen poisoned Yang Zan.

Late in Emperor Wen's reign

In 595, the luxurious summer vacation palace, Renshou Palace (仁壽宮, in modern Baoji, Shaanxi), was completed by the general Yang Su. When the frugal Emperor Wen saw how luxurious the palace was, he was unhappy and angrily stated, "Yang Su expanded the efforts of the people to construct this palace. The people will despise me." Soon thereafter, however, when Empress Dugu arrived at the palace as well, she advised Emperor Wen to comfort Yang Su, and when he subsequently summoned Yang Su to the palace, she stated, "You know that this old couple had little to enjoy, so you decorated this palace in this way. Is it not that in doing so, you are being both faithful and filial?" She gave him a large award of money and silk.

In 598, Empress Dugu and her younger brother, Dugu Tuo (獨孤陀), born of different mothers, were embroiled in a mysterious scandal. It was said that Dugu Tuo, whose wife was a sister of Yang Su's, had a female servant named Xu Ani (徐阿尼), who worshipped cat spirits and was capable to have those spirits kill people for her. At this time, both Empress Dugu and Yang Su's wife, Lady Zheng, was seriously ill, and it was suspected that they were afflicted by cat spirits. Emperor Wen suspected Dugu Tuo and had the official Gao Jiong investigate and Gao reported that it was indeed Dugu Tuo who instigated the matter. Emperor Wen ordered Dugu Tuo and Lady Yang to commit suicide, but Empress Dugu went on a three-day hunger strike to try to save them, stating, "If Tuo had harmed the people, I would not dare to say anything, but his crime was on my account, and therefore I dare to beg you to spare his life." Dugu Tuo's younger brother, Dugu Zheng (獨孤整), also pleaded earnestly, and Emperor Wen spared them, reducing Dugu Tuo to commoner rank and forcing Lady Yang to become a Buddhist nun.

Over the years, the relationship between Emperor Wen and Empress Dugu was still largely loving. However, on one occasion, when Emperor Wen happened to see the beautiful granddaughter of Yuchi Jiong, who had been forced into slave labor after her grandfather's death, he had sexual relations with her. When Empress Dugu found out, she had Lady Yuchi killed. In anger, Emperor Wen rode away from the palace on a horse and refused to return. Gao Jiong and Yang Su had to track him down and urge him to return to the palace, with Gao stating, "Your Imperial Majesty, how can you abandon the empire on account of a woman?" When Emperor Wen did return to the palace after midnight, Empress Dugu was still waiting for him, and she wept and begged him for forgiveness. Gao and Yang Su subsequently hosted a banquet for them, and their differences went away.

When Empress Dugu heard that Gao Jiong, whom she had respected previously, refer to her as "a woman," she became secretly resentful of him. Later, she became particularly angry at Gao over his marital relations, as after his wife died, she suggested Emperor Wen find him another wife, but he declined, stating that he was getting old and beginning to lose sexual urges and did not need another wife—and soon thereafter, his concubine bore a son. Empress Dugu pointed out that, in effect, he was not truthful, and Emperor Wen began to distance himself from Gao. Further, in 598, when Gao, under Emperor Wen's duress, was forced to accompany Yang Liang, the Prince of Han, in a campaign against Goguryeo, a campaign that he opposed, the campaign ended in failure, and Empress Dugu blamed him for the failure, particularly after Yang Liang, angry that Gao was not following his orders, complained to her.

Another person who began to draw Empress Dugu's ire was her son, Yang Yong, the Crown Prince. When he was young, Emperor Wen and Empress Dugu had selected for him a wife from the honored Yuan clan, Northern Wei's imperial clan—the daughter of the official Yuan Xiaoju (元孝鉅). However, Yang Yong did not favor Crown Princess Yuan, and instead had many concubines, including his favorite Consort Yun, and he did not have any sons with Crown Princess Yuan. When the Crown Princess died in 591 after a brief illness, Empress Dugu suspected Yang Yong and/or Consort Yun of poisoning her, and rebuked Yang Yong.

The second son of Emperor Wen and Empress Dugu, Yang Guang, the Prince of Jin, who had ambitions of displacing his older brother, put on pretenses of living frugally (which pleased Emperor Wen) and loving no one but his wife Princess Xiao (which pleased Empress Dugu).

By 599, both Emperor Wen and Empress Dugu were considering replacing Yang Yong with Yang Guang, but when Empress Dugu once approached Gao with the issue, he stated firmly that the Crown Prince should not be replaced. Therefore, Empress Dugu suggested that Emperor Wen remove Gao and he was accused of crimes, removed from his office and reduced to commoner rank.

Meanwhile, Yang Guang was continuing to provoke Empress Dugu, falsely stating that he feared that Yang Yong would eventually put him to death. Yang Guang further entered into an alliance with Yang Su, with whom Yang Yong had a poor relationship, and Empress Dugu also told Yang Su to encourage Emperor Wen to depose Yang Yong. Subsequently, Yang Guang engaged Yang Yong's associate, Ji Wei (姬威), to falsely accuse Yang Yong of plotting treason.

In 600, after an investigation conducted by Yang Su, in which he manufactured evidence against Yang Yong, Emperor Wen deposed the Crown Prince and put him under house arrest, replacing him with Yang Guang.

In fall 602, Empress Dugu died, and Emperor Wen was greatly saddened, although he was comforted by Wang Shao (王劭), who submitted a petition in which he tried to use prophecies to show that Empress Dugu was, in fact, a Bodhisattva.