<p>This study aimed to explore the association between handgrip strength and all-cause mortality risk among patients receiving maintenance peritoneal dialysis (PD). This prospective cohort study enrolled adult patients with kidney failure undergoing PD, with regular follow-up conducted from January 2022 to March 2025. Baseline handgrip strength was the exposure of interest, and all-cause mortality during follow-up was set as the primary endpoint. Kaplan–Meier survival curves with the log-rank test were used to compare survival differences across groups. Multivariable Cox proportional hazards regression models were applied to adjust for potential confounding factors. A total of 258 participants with complete baseline data were included in the final statistical analysis. Overall, 57.8% (149/258) of participants exhibited low handgrip strength. Over the 3-year follow-up period, 3.9% (10/258) of participants were lost to follow-up after switching to hemodialysis, and 18.5% (55/258) experienced all-cause death. Mortality was 28.2% (42/149) in the low handgrip strength group versus 11.9% (13/109) in the normal handgrip strength group, with an absolute mortality difference of 16.3% (95% CI 6.9–25.7%) between groups. Cardiovascular disease accounted for 80.0% of all recorded deaths. Kaplan–Meier survival curves indicated worse survival among participants with low handgrip strength (log-rank test, χ² = 10.22, <i>P</i> = 0.001). Multivariable Cox proportional hazards regression models adjusting for relevant confounders were applied to assess the association between handgrip strength and all-cause mortality (low vs. normal handgrip strength). After full adjustment for potential confounding factors, low handgrip strength remained significantly associated with higher all-cause mortality risk (HR 2.35, 95% CI 1.25–4.41, <i>P</i> = 0.008). Given cardiovascular disease represented the leading cause of death in this cohort, we performed a sensitivity analysis taking cardiovascular mortality as the primary endpoint. The association between handgrip strength and cardiovascular mortality was consistent with the primary analysis (HR 2.48, 95% CI 1.22–5.03, <i>P</i> = 0.012). Furthermore, a post-hoc sensitivity analysis was conducted using the updated 2025 AWGS age-stratified cut-offs to validate result stability. After rigorous multivariable adjustment, the robust association between low handgrip strength and elevated all-cause mortality risk persisted (HR 6.53, 95% CI 1.56–27.36, <i>P</i> = 0.01). Low handgrip strength is independently correlated with higher all-cause mortality risk in patients receiving maintenance PD. Handgrip strength may serve as a simple, practical prognostic marker for risk stratification in this population.</p>