Breast cancer (BC) is one of the most commonly diagnosed types of cancer in women. Oxidative stress may contribute to cancer etiology through several mechanisms. A large body of evidence indicates that physical activity (PA) has positive effects on different aspects of BC evolution, including mitigation of negative effects induced by medical treatment. With the aim to verify the capacity of PA to counteract negative effects of BC treatment on systemic redox homeostasis in postsurgery female BC patients, we have examined the modulation of circulating levels of oxidative stress and inflammation markers. Moreover, we evaluated the impacts on physical fitness and mental well-being by measuring functional parameters, body mass index, body composition, health-related quality of life (QoL), and fatigue. Our investigation revealed that PA was effective in maintaining plasma levels of superoxide dismutase (SOD) activity and tGSH, as well as peripheral blood mononuclear cells’ (PBMCs) mRNA levels of SOD1 and heat-shock protein 27. Moreover, we found a significant decrease in plasma interleukin-6 (≈0.57 ± 0.23-fold change,p< 0.05) and increases in both interleukin-10 (≈1.15 ± 0.35-fold change,p< 0.05) and PBMCs’ mRNA level of SOD2 (≈1.87 ± 0.36-fold change,p< 0.05). Finally, PA improves functional parameters (6 min walking test, ≈+6.50%,p< 0.01; Borg, ≈−58.18%,p< 0.01; sit-and-reach, ≈+250.00%,p< 0.01; scratch right, ≈−24.12%, and left, ≈−18.81%,p< 0.01) and body composition (free fat mass, ≈+2.80%,p< 0.05; fat mass, ≈−6.93%,p< 0.05) as well as the QoL (physical function, ≈+5.78%,p< 0.05) and fatigue (cognitive fatigue, ≈−60%,p< 0.05) parameters. These results suggest that a specific PA program not only is effective in improving functional and anthropometric parameters but may also activate cellular responses through a multitude of actions in postsurgery BC patients undergoing adjuvant therapy. These may include modulation of gene expression and protein activity and impacting several signaling pathways/biological activities involved in tumor-cell growth; metastasis; and inflammation, as well as moderating distress symptoms known to negatively affect QoL.