Objective: To explore the application effect of oral care combined with psychological intervention on improving patients’ oral hygiene and alleviating negative emotions. Methods: A total of 78 patients admitted to the hospital between January and December 2023 were recruited and divided into two groups using a random number table method, each group consists of 39 cases. The control group received routine care, while the study group received oral care combined with psychological intervention. Oral health scores and the patients’ negative emotional states were compared between the two groups. Results: The oral health score of the study group (35.66 ± 5.69) was significantly better than that of the control group (26.36 ± 6.21; P < 0.05). Additionally, the depressed mood and anxiety scores of the study group (27.69 ± 6.12 and 26.36 ± 6.21, respectively) were significantly lower than those of the control group (36.23 ± 5.98 and 35.66 ± 5.69, respectively; P < 0.05). Conclusion: Clinical research combining routine care, psychological intervention, and oral care has revealed that the combined approach significantly enhances patients’ treatment adherence, alleviates negative emotions, and improves their quality of life.