Leishmaniasis is a disease caused by over 20 species of protozoa of the genus Leishmania, transmitted by the bite of infected phlebotomine sandflies. This parasitic infection has an anthropozoonotic nature, affecting both wild and domestic animals, as well as humans. It may present itself as three main clinical forms: cutaneous, mucocutaneous, or visceral leishmaniasis. The interaction between the parasite and the host's immune system is complex, involving evasion mechanisms primarily through the modulation of oxidative stress. Leishmania lacks several antioxidant enzymes common to mammals; instead, it relies on a few alternative redox systems, such as the trypanothione family which is essential for counteracting reactive oxygen and hydrogen species within phagolysosomes of neutrophils and macrophages. These mechanisms also modulate the composition and pH of the parasitophorous vacuole, preventing the efficient elimination of the amastigote forms from host cells. Additionally, the parasite induces cytoskeletal and metabolic changes in mammalian host cells to promote a favorable microenvironment for its survival. Given these aspects, this review discusses Leishmania's oxidative stress evasion strategies, focusing on both parasite-specific adaptations and their effects on host metabolism and immune response, whether in macrophages, neutrophils, or dendritic cells; as well as the role of oxidative stress in canine visceral leishmaniasis. A deeper understanding of these mechanisms may support the development of novel therapeutic approaches, such as drugs targeting oxidative response modulation and improved vaccination strategies.