Objective: To evaluate the application effect of an individualized comprehensive oral care intervention program in adult mechanically ventilated patients in the ICU an evidence-based basis for clinical oral care. Methods: A total of 80 adult mechanically ventilated patients in the ICU of a tertiary hospital from January to December selected and randomly divided into a control group and an observation group, with 40 cases in each group. The control group received routine oral care, while the observation group received incomprehensive oral care. The intervention continued until the patients were extubated or transferred out of the ICU. SPSS 26.0 software was used for analysis. Measure was expressed as (± s) and analyzed using t-tests; count data were expressed as [n(%)] and analyzed using χ² tests. p < 0.05 was statistically significant. Results: After the intervention, the oral hygiene score (2.15 ± 0.62), VAP incidence rate (7.50%, 3/40), and total incidence rate of oral complications (5.00%, 2/40) in the observation group were significantly lower than those in the control group (4.82 ± 0.95, 25.00%, 10/40, and 22.50%, 9/40, respectively) (all p < 0.05). The duration of mechanical ventilation (6.82 ± 2.15 days) and ICU length of stays (10.35 ± 3.26 days) in the observation group were significantly shorter than those in the control group (p < 0.001). Conclusion: Individualized comprehensive oral care improves oral hygiene in adult mechanically ventilated patients in the ICU, reduce the incidence of VAP and oral complications, and shorten the duration of mechanical ventilation and ICU length of stay, demonstrating clinical value.