The purpose of this study was to investigate the effect and mechanism of 3% boric acid solution (BAS) against Candida albicans (CA) infection via the interleukin-23 (IL-23)/T helper 17 cell (Th17) axis. 36 female mice were randomly divided into 3 groups, and 2 injection sites on the back of the mice were chosen at random. Group N was injected with sterile water for injection (SWFI), and Group M and Group B were injected with CA mycelium suspension. After successful model verification, the remaining mice entered the following treatments 5 days later. Group B was treated with 3% BAS, Group M was treated with SWFI, and Group N was not treated. Levels of interleukin-17 (IL-17), IL-22, and IL-23 in mouse blood were measured on days 1, 3, 5, and 7 of treatment. On day 7, IL-17, IL-22, and IL-23 in mouse skin were detected. Serum levels of IL-17, IL-22, and IL-23 in Group M were higher than in Group N on the first day of treatment (p < 0.05). Expression levels of IL-17, IL-22, and IL-23 in the epidermis of the skin lesions in Group M were higher than in Group N on day 7 (p < 0.05). The serum level of IL-17 in Group B was higher than in Group M on days 5 and 7 (p < 0.05). Serum levels of IL-22 in Group B on days 1, 5, and 7 were higher than in Group M (p < 0.05). Serum levels of IL-23 in Group B were higher than in Group M on days 3, 5, and 7 (p < 0.05). IL-17 and IL-23 in Group B reached a peak on day 5, significantly different on days 1, 3, and 7 (p < 0.05). The expression intensity of IL-17, IL-22, and IL-23 in the skin lesions of Group B was higher than that of Group M on day 7 (p < 0.05). We conclude that IL-17, IL-22, and IL-23 are involved in the anti-CA activity in mouse skin, and 3% BAS increased IL-17, IL-22, and IL-23 to mediate these effects.