This meta-analysis aims to assess the efficacy of combining clotrimazole and metronidazole in the treatment of mixed infectious vaginitis (VA). The goal is to provide clinical guidance for future medication strategies. We conducted a comprehensive search of the literature database for studies involving the use of clotrimazole combined with metronidazole in the treatment of mixed infectious VA. After rigorous screening, eligible studies were subjected to meta-analysis using RevMan 5.3 software. Outcome measures included cure rates, recurrence rates, and the incidence of adverse reactions. Six randomized controlled trials (RCTs) were included, comprising 160 patients in the test group (treated with clotrimazole combined with metronidazole) and 160 patients in the control group (treated with alternative regimens). All selected studies were of high quality and possessed significant reference value. Meta-analysis results indicated that, in comparison to the control group, the test group exhibited a comparable incidence of adverse reactions (P > .05), higher cure rates, increased treatment satisfaction, and a lower recurrence rate (P < .05). The combination of clotrimazole and metronidazole is an effective treatment option for mixed infectious vaginitis, thus warranting recommendation.