Objective The influence of diabetes mellitus (DM) on mortality following lower extremity amputation (LEA) remains controversial. This systematic review and meta-analysis aimed to determine the influence of DM on longterm mortality (LTM) and short-term mortality (STM) after amputation. Materials and methods The Medline, the Cochrane library, and Embase databases were searched. The primary and secondary outcomes were LTM and STM following amputation. One-year and 30-day all-cause mortality after amputation were considered as LTM and STM, respectively. A random-effects model was utilized to pool results. To evaluate the stability of results, subgroup analyses and sensitivity analyses were conducted. Results Twenty-three cohort studies with a total of 58,219 patients were included, among which 31,750 (54.5%) patients had DM. The mean score of included studies evaluated by Newcastle-Ottawa Scale was 7.65, indicating moderate to high quality. The pooled results showed no significant difference in 1-year LTM (risk ratio [RR], 0.96; 95% CI 0.86-1.07) after amputation. However, 3-year (RR, 1.22; 95% CI 1.01-1.47) and 5-year (RR, 1.18; 95% CI 1.07-1.31) LTMs of DM patients were obviously higher than that of NDM (non-diabetes mellitus) patients. The STM of the DM group was significantly lower than the NDM group (RR, 0.80; 95% CI 0.64-0.98). Conclusions The current study revealed that DM patients had an obvious lower STM following LEA, but the risk of DM on LTM after amputation was gradually increased with time. More attention should be paid to the long-term survival of DM patients after LEA.