Objective To analyze the effect of four-handed operation combined with whole-course reffned nursing on oral health status in patients undergoing oral rehabilitation. Methods A total of 150 patients who received oral rehabilitation in the Department of Stomatology, Rugao Bo'ai Hospital from January to December 2024 were selected as the research subjects. According to the random number table method, they were divided into the control group and the observation group, with 75 patients in each group. The control group was given conventional nursing, and the observation group was given four-handed operation combined with whole-course refined nursing. The oral health status, plaque index, gingival index, cross-infection and nursing comfort were compared between the two groups. Results After nursing, the scores of pain, language limitation and masticatory function in the observation group were higher than those in the control group (P<0.05). After nursing, the scores of PLI and GI in the observation group were lower than those in the control group (P<0.05). The incidence of cross-infection in the observation group (1.33%) was lower than that in the control group (9.33%) (P<0.05). After nursing, the scores of nursing comfort in the observation group were better than those in the control group (P<0.05). Conclusion Four-handed operation combined with whole-course reffned nursing can effectively maintain the periodontal health of patients undergoing oral rehabilitation. It not only reduces the plaque index, gingival index and the risk of cross-infection, but also comprehensively improves the treatment comfort of patients.