With the intensification of global population aging, osteoarthritis (OA) has emerged as a major socioeconomic burden requiring urgent therapeutic interventions. Low-intensity pulsed ultrasound (LIPUS), a non-invasive physical therapy modality, delivers pulsed acoustic energy to target tissues with negligible thermal effects. Accumulating evidence from preclinical studies and randomized controlled trials has demonstrated its potential to decelerate OA progression. This systematic review synthesizes current knowledge on LIPUS-mediated OA management, elucidates mechanistic pathways through biomechanical and molecular analyses, strategies combining LIPUS with biomaterials to improve its efficacy, evaluates clinical translation challenges, and proposes standardized treatment protocols to optimize therapeutic outcomes.