Several drug release studies are continuously carried out to minimize pharmacological limitations, such as insolubility in water and gastrointestinal irritability. This study focused on the development of gels for the administration of amphotericin-B (AmB) for the treatment of cutaneous leishmaniasis. Two gels were prepared from copolymers (polyglycerol and ε-caprolactone) incorporated with AmB. The gels were characterized by FTIR, NMR, TG, and DSC techniques. The incorporation of AmB into the copolymers showed that the medicine remained in the monomeric form, which is the least toxic. The AmB loading presented values of about 31 % (w:w) for TMP-HPG-PCL and for GLY-HPG-PCL, while the encapsulation efficiency was 93 % for both copolymers. According to the release profile, it is observed that, after 48 h, the percentage of AmB released for pure amphotericin, TMP-HPG-PCL-AmB, and GLY-HPG-PCL-AmB were 100 % ± 6 %, 100 % ± 1.5 %, and 47 % ± 13, respectively. Hemolytic study, Cytotoxic Evaluation showed that TMP-HPG-PCL and GLY-HPG-PCL were not toxic to both cell lines (HaCat and MCF-7). These results suggest that the copolymers are safe for in vivo applications being able to act as a drug carrier that have low water solubility corroborating their purpose of polymeric support in the transport of drugs. TMP-HPG-PCL-POL-AmB and for GLY-HPG-PCL-HPG-POL-AmB were used in female mice (BALB/c) infected with Leishmania major foremost for 40 days, and it was found that in animals treated with the gel/copolymer/AmB, there was a reduction in the number of parasites of around 70 %. Histopathological studies showed the presence of small intralobular granulomas and moderate Kupffer cell hypertrophy/hyperplasia. The results show that the TMP-HPG-PCL-POL-AmB and for GLY-HPG-PCL-HPG-POL-AmB efficiently combats cutaneous leishmaniasis.