This perspective article emphasizes the significant role of reactive oxygen species (ROS) in in vivo remedial therapy of various diseases and complications, capitalizing on their potential reactivity. Among the various influencers, herein, piezoelectric materials driven ROS generation activity is primarily considered. Intrinsic non-centrosymmetry of piezoelectric materials makes them suitable for distinct dipole formation in the presence of external mechanical stimuli. Such characteristics prompt the positioning of opposite charged carriers to execute associated redox transformations that effectively participate to generate ROS in the aqueous media of the cell cytoplasm, organelles and nucleus. The immense reactivity of piezoelectric material driven ROS is fostered to terminate cellular toxicity or curtail tumor cell growth, due to their higher specificity. This perspective considers the conjugated performance of piezoelectric materials and ultrasound which can remotely generate electrical charges that promote ROS production for therapeutic application. In particular, a substantial synopsis is provided for the remedial activity of numerous piezocatalytic materials in tumor cell apoptosis, antibacterial treatment, dental care and neurological disorders. Subsequently, the report precisely demonstrates the methods involving various spectrophotometric approaches for the analysis of the ROS. Finally, the key challenges of piezoelectric material-based therapy are discussed and systematic future progress is outlined.