BACKGROUND: The Mediterranean diet (MD) exerts a protective effect against cancer development and progression; however, the evaluation of its impact on gastric cancer still remains quite scarce. The present study aims to evaluate the association of MD adherence during the lifespan with disease progression characteristics, lifestyle factors and overall survival in gastric carcinoma patients. METHODS: This is an observational, cross-sectional study conducted on 186 gastric cancer patients followed up for a median time interval of 57 months or until death due to cancer disease. Tumor histopathological characteristics were retrieved from patients' medical records, while validated questionnaires assessing, immediately after the time of diagnosis, health-related quality of life, physical activity levels, sleep quality, depression, anxiety and MD adherence during the lifespan were used. RESULTS: Higher MD adherence during the lifespan was significantly associated with younger patients (p = 0.0106), regular smoking (p < 0.0001), abnormal BMI status (p < 0.0001), intestinal-type gastric carcinoma (p = 0.0111), high tumor histopathological grade (p < 0.0001) and earlier disease stage (p < 0.0001). Moreover, patients with elevated MD adherence during their lifespan showed significantly better health-related quality of life (p < 0.0001), higher physical activity levels (p < 0.0001), more adequate sleep quality (p < 0.0001) and lower prevalence of depression (p = 0.0003) and anxiety (p = 0.0006) compared to those with reduced MD adherence. In multiple regression analysis, elevated MD compliance during the lifespan was independently correlated with longer overall patient survival after adjustment for several confounders (Cox regression analysis, p = 0.0001). CONCLUSIONS: Higher MD adherence during the lifespan was associated with less advanced tumor histopathology characteristics and favorable mental and physical lifestyle factors. Moreover, higher MD adherence during the lifespan was also independently correlated with longer overall survival in gastric carcinoma patients. Thus, adopting a healthy dietary pattern like the MD during the lifespan may act as a preventive agent in combination with a healthy lifestyle against gastric cancer development and progression.