There were limited data investigating platelet indices in predicting peritoneal dialysis (PD) outcomes on comorbidities. The aim of this study was to evaluate the association between platelet indices and new-onset comorbidity and all-cause mortality in PD patients. A single-center, retrospective observational cohort study was conducted in incident PD patients from 28 December 2011 to 24 January 2018, and followed up until 31 December 2022. Time to the first new-onset cardiovascular disease (CVD) and time to the first new-onset infection event after PD were identified as the primary outcomes. All-cause mortality was identified as the secondary endpoint. The correlation between platelet indices and comorbidities and all-cause mortality were assessed by Cox model. Data of liver disease status was not collected and analyzed. Survival curves were performed by Kaplan-Meier method with log-rank tests. A total of 250 incident PD patients with a median follow-up of 6.79 (inter-quarter range 4.05, 8.89) years was included. A total of 81 and 139 patients experienced the first new-onset CVD and infection event respectively during the follow-up period. High mean platelet volume (MPV) was independently associated with high risk of time to the first new-onset CVD (HR 1.895, 95% CI 1.174-3.058, p = 0.009) and all-cause mortality (HR 1.710, 95% CI 1.155-2.531, p = 0.007). Patients with low mean platelet volume to platelet count ratio (MPV/PC) were prone to occur the new-onset infection events (log rank 5.693, p = 0.017). Low MPV/PC (HR 0.652, 95% CI 0.459-0.924, p = 0.016) was significantly associated with the time to the first new-onset infection event on PD. Platelet indices were associated with the new-onset CVD, infectious comorbidities and all-cause mortality on PD. Low MPV/PC was associated with time to the first new-onset infection event in PD patients. Moreover, high MPV was associated with new-onset CVD and all-cause mortality in the incident PD patients.