Cutaneous lesions are a common pathology encountered in teleosts housed in both public and home aquariums. This study aimed to investigate the efficacy of medical grade honey, 0.03% naltrexone, and compounded 2% polyoxethylene with neomycin sulfate on skin lesions using redbelly yellowtail fusiliers (Caesio cuning) as a model. Polyoxethylene is a water-soluble polymer that has been used as a gel bandage for the treatment of wounds in fish, but there is limited primary literature evaluating it’s efficacy as a topical treatment. Punch biopsies were generated on six fish per treatment group under anesthesia. Treatment groups received one of the following topical medications after wounding: MediHoney ® gel, 0.03% naltrexone ointment, or compounded 2% polyoxethylene with neomycin sulfate. Nontreated positive control groups were similarly wounded but did not receive topical treatment. Fish were housed at 75°C. Treatment was repeated every 48 hours for the first 2 weeks and then every 4 days for an additional three treatments. There was an overall improvement in macroscopic appearance in compounded 2% polyoxethylene with neomycin sulfate-treated groups compared with positive controls on day 14 after wounding (P = 0.001), whereas with the treatment groups not receiving compounded 2% polyoxethylene with neomycin sulfate, wounds had increased inflammation grades (P < 0.0001 and P < 0.0001, respectively) with enlarged wound areas (P < 0.0001 and P < 0.001, respectively) in comparison with positive controls. This study suggests that topical use of compounded 2% polyoxethylene with neomycin sulfate produces positive effects on wound healing.