Objective To observe the efficacy and safety of clioquinol cream combined with adapalene gel in the treatment of acne vulgaris. Methods A total of 98 patients with acne vulgaris admitted to our hospital from May 2020 to April 2021 were selected as the research objects and divided into treatment group (52 patients) and control group (46 patients) according to the random number table method. The treatment group was treated with clioquinol cream combined with adapalene gel, and the control group was treated with fusidic acid cream combined with adapalene gel. The clinical efficacy and adverse reactions were compared between the two groups. Results The total effective rate of the treatment group was higher than that of the control group (P<0.05). There was no significant difference in the incidence of adverse reactions between the two groups (P>0.05). Conclusion Clioquinol cream combined with adapalene gel is effective and safe in the treatment of acne vulgaris, which is worthy of clinical application.