Cutaneous leishmaniosis (CL) is an important parasitic disease characterized by specific skin lesion, includes the vector that cause the CL and treatment in general. The study aimed to identify the effect of three different drugs which are β-sitosterol, ketoconazole 2% and mupirocin in the treatment of cutaneous leishmaniosis. The study was conducted at Dermatological Unit of Al Hussein Teaching Hospital/Thi-Qar/Iraq from October to November 2021. The patients presented with a lesion will be involved in this study and its involved isolation of parasites from the lesion of patients and the parasite was replicated in (NNN) media then the inoculum was concentered. A total of 40 male of mice (Mus musculus) of BALB/c strain injected by parasite suspension, after the appearance of lesion, β-sitosterol, ketoconazole 2% and mupirocin was applied on a lesions daily for 2 weeks, the statistical analysis was done by SPSS program. In the current study, the β-sitosterol was most effective in the treatment of skin leishmanial lesion than the other drugs with mean is (11.9±1.449 mm) in compared with the other drugs under P-value < 0.046 with the complete recovery. β-sitosterol was highly effect on the L. tropica infections with complete recovery and no scar appearance than ketoconazole and mupirocin and can be used for treatment of the disease lesion.