Oxidative stress, a condition induced by an excessive amount of free radicals, such as reactive oxygen species (ROS), shows several gender-related differences in basal cellular redox state and antioxidant responses. Crenotherapy with sulfureous mineral water can improve the cellular redox state. In this retrospective observational study, gender-related differences in the efficacy of sulfureous crenotherapy in decreasing oxidant species were investigated. Seventy-eight patients, stratified by sex, with osteoarthritis or degenerative joint disease and Vulgar psoriasis who have received a cycle of sulfureous mud-bath therapy + sulfureous hydropinotherapy were enrolled. Plasma concentration of oxidant species and clinical outcomes were measured at baseline and at the end of treatment. After 2 weeks of sulfureous crenotherapy, a significant amelioration of clinical outcomes and a significant reduction of oxidant species were observed in both sexes, more marked in females than in males (p = 0.0001 and p = 0.04, respectively). For patients with high oxidant species at baseline, females showed a greater reduction in itching compared to males (−95% vs. −50%), while men had a higher amelioration in pain and morning stiffness (−45% vs. −32%, and −50% vs. −37%, respectively). In conclusion, sulfureous crenotherapy can be a valuable strategy to improve cellular redox state in both sexes.