: The Pearl River Delta (PRD) region in Guangdong, China, is urbanized and economically significant. Rapid development has shaped diverse dietary habits. In this densely populated area, there is an urgent need to assess vitamin status and its impact on age-related diseases. : A total of 2646 participants (age: 50.92 ± 9.30 years; male: 64.06%) were recruited from the Pearl River Delta (PRD) region. Participants were included from 1 December 2020 to 30 November 2021. Three restricted cubic spline logistic models, interaction terms, and mediated effects analyses were used to assess the association between vitamin A, B, E, B, B, B, B, B, and B between five age-related diseases: cerebrovascular disease (CVD), coronary heart disease (CHD), hypertension (HTN), dyslipidemia (DYS), and type 2 diabetes mellitus (T2DM). : Blood concentrations of nine vitamins showed a right-skewed distribution. Significant correlations were found between vitamin levels and age-related diseases across nine groups ( < 0.05). A J-shaped relationship was observed between vitamin levels and the risk of age-related diseases, except for the Vitamin A-HTN/T2DM, which showed Maximum Effective Concentration (MEC). Specific thresholds included: Vitamin A: 1080 ng/mL (DYS); Vitamin B: 77 ng/mL (CVD), 75.5 ng/mL (HTN); Vitamin B: 900 ng/mL (CVD), 600 ng/mL (HTN), 690 ng/mL (DYS); Vitamin B: 82 ng/mL (CVD). The protective effect of vitamins against age-related diseases decreased with age, and higher levels of vitamins A and B correlated with increased hypertension risk in older adults (P < 0.01). Low Body Resilience Index (BRI) and physical activity mediated the protective effects of vitamins A and B on HTN and DYS, while no mediating effects were found for smoking and alcohol consumption. : The effectiveness of multivitamin supplementation in preventing cardiovascular, cerebrovascular, and metabolic diseases may be limited in healthy aging populations. Health professionals should consider patients' physiological conditions and blood vitamin levels to avoid overdose. More interventional studies are needed to establish causal relationships.