Due to its regenerative action, extracorporeal shock wave therapy (ESWT) is applied in treating integumentary and musculoskeletal diseases. However, other potential therapeutic interventions are being investigated. It is essential to fully understand its mitochondrial signaling pathway to achieve this, which plays a fundamental role in elucidating the mechanism of action and possible therapeutic interventions. Thus, this study aimed to analyze the effect of ESWT on mitochondrial pathways through the relationship between lipolysis and adipocyte apoptosis, as well as cellular functionality. This is a non-randomized case-control clinical trial where obese women received ESWT sessions in the abdominal region, after which tissue samples were collected for histological and immunohistochemical analyses of adipose tissue. The data demonstrated positivity in the expression of mitochondrial markers related to cell apoptosis, such as FIS1 (p < 0.0203) and OPA1 (p < 0.0283), in addition to the positivity of anti-MFN1, responsible for regulating mitochondrial cell proliferation (p < 0.0003). In summary, this study demonstrates that ESWT was able to activate specific mitochondrial signaling pathways, which may be associated with its ability to stimulate lipolysis and apoptosis in superficial adipose tissue. However, no significant improvements in cellular functionality were observed.