Objective To perform a systematic review to evaluate the impact of deprescribing interventions on the clinical outcomes in the elderly patients with polypharmacy. Methods A thorough search was made in the databases of the literature related to deprescribing interventions in the elderly patients with polypharmacy. The studies were screened according to the inclusion and the exclusion criteria. I² test for heterogeneity among studies was performed using Review Manager 5.3. Fixed effect model or random effect model was employed to analyze the impact of deprescribing interventions in the elderly patients with polypharmacy. Results A total of 18 studies were selected for the final randomized controlled trials (RCT), with overall quality of the literature being good. Meta-analysis showed that deprescribing interventions were not able to decrease all-cause mortality among elderly patients with polypharmacy [OR=0.86, 95%CI (0.67-1.09)]. The comparison between different intervention methods showed that patient-specific interventions decreased all-cause mortality [OR=0.68, 95%CI (0.51-0.92)]. The comparison of the follow-up length showed that long follow-up (>6 months) outperformed shorter follow-up (≤6 months) in decreasing all-cause mortality [OR=0.58,5%CI (0.39-0.86) vsOR=1.02, 95%CI (0.76-1.36); P＜0.05]. The comparison between different age groups showed no change in all-cause mortality [OR=0.63,5% CI (0.40-1.02) vs OR=0.95,5%CI (0.72-1.25); P＞0.05]. The comparison of cognitive status showed that deprescribing interventions in the groups of different cognitive statuses did not alter all-cause mortality [OR=0.63,5%CI(0.37-1.07) vs OR=0.93, 95%CI (0.71-1.22); P>0.05]. Deprescribing interventions did not decrease the number of patients with[JP+1]falls [OR=0.98, 95%CI (0.74-1.27)] but were able to significantly decrease the average falls they experienced [MD=-0.11,95%CI (-0.21--0.02)] and the length of hospital stay [MD=-0.49,5%CI (-0.76--0.22)]. Conclusion The analysis of data available suggested that deprescribing interventions did not decrease all-cause mortality in elderly patients with polypharmacy, but patient-specific or long-term follow-up seemed to have an advantage in decreasing it; that deprescribing interventions did not decrease the number of patients with falls but reduced the number of falls they experienced and the length of hospital stay. Patient-specific deprescribing interventions seem to be safe and feasible in decreasing inappropriate polypharmacy.