The present narrative review aims to highlight the possible effects manual therapies could have on cells and mitochondria, as these effects could improve athletic performance management. To this aim, this review summarizes the relationship between mechanical stimulation, with a special focus on physical activity, and cell response based on the most recent mechanobiology findings. Mechanobiology analyzes how cells respond to mechanical stressors coming from the environment. Indeed, endogenous (e.g., blood pressure, heartbeat and gastrointestinal motility) and exogenous (e.g., physical activity and manual therapies) stimuli can induce biochemical and epigenetic modifications that alter protein synthesis with heavy consequences on cell behavior. Mechanical stress can also influence mitochondrial behavior (i.e., biogenesis, autophagy, fusion, fission and energy production), sarcoplasmic response and calcium ion (Ca2+) flux. Since manual therapies have been shown to affect the extracellular matrix, which represents a primary source of mechanical stress that may alter both the cytoskeleton and mitochondrial metabolism, it is conceivable manual therapies could also affect cellular and mitochondrial behavior. Lastly, by suggesting possible directions for future laboratory and clinical studies, the authors expect this review to inspire further research on how manual therapies could affect bioenergetic metabolism and, thus, athletic performance.