Objective: Healthspan refers to the length of time an individual maintains good physical and mental health without serious chronic diseases or functional impairments. In recent years, the role of dietary factors in extending healthspan has received extensive attention. Cheese is considered as a healthy food but its effect on healthspan and remains unknown. This study aims to clarify the association between cheese intake and healthspan, and and further explore the underlying metabolic mechanisms. Methods: This study employed a nested case-control design and defined healthspan terminated (HST) based on eight reported sub-events of HST in UK Biobank (UKB). 93 214 HST participants and 279 642 controls were included. Conditional logistic regressions was used to evaluate the association between cheese intake and HST, and Mendelian randomization (MR) was used to assess the causal effect. Furthermore, we explored the mediating role of metabolites in this relationship by Two-step MR and observational analysis. Results: Cheese intake is a protective factor for healthspan (Ptrend＜0.05). Specifically, participants with high cheese intake (>5 times/week) had a lower risk of HST (OR=0.93, 95% CI: 0.89-0.98) compared to those who never intake cheese. MR analysis confirmed this protective effect. Mediation analysis suggested that plasma high density lipoprotein cholesterol (HDL-C) and glucose mediated 6.33% and 14.82% of this effect, respectively. Conclusion: These findings suggested that cheese intake might improve the healthspan by decreasing plasma glucose and increasing plasma HDL-C. As an important component of healthy diet, cheese intake might be recommended in our daily diet structure.