Objective/Purpose Women at reproductive age frequently experience vulvovaginal infections and vaginitis. The most common etiologies are vulvovaginal candidiasis (VVC), bacterial vaginosis (BV), desquamative inflammatory vaginitis/aerobic vaginitis, and trichomoniasis. Various treatment options are available for these infections, such as specific antimicrobial or antiseptic agents. Dequalinium chloride (DQC) is a local antiseptic agent with a broad antimicrobial and antifungal spectrum. Multiple studies suggest that DQC is an efficient treatment for vaginal infections; however, it is not widely recommended as a first-line treatment. This systematic review and meta-analysis aims to evaluate the efficacy of DQC compared with that of standard treatment. Methods Our systematic review was conducted according to the PRISMA guidelines. PubMed/MEDLINE, EMBASE, CENTRAL, and clinicaltrials.org were searched to retrieve relevant reports up to October 2022. Results Four randomized controlled studies and 1 observational study were included in this review. Overall, DQC showed noninferiority to the reference treatments for BV and VVC, and to the evaluated treatment options for desquamative inflammatory vaginitis/aerobic vaginitis. For BV and VVC, this could also be confirmed in a meta-analysis including 3 randomized controlled studies. No serious adverse events were reported in any of these studies. Conclusions Dequalinium chloride offers a safe, well-tolerated, and efficient treatment option for vulvovaginal infections of different etiologies. However, further studies are needed to confirm our findings and allow inclusion of DQC as a first-line treatment into guidelines.