Background: Oxymatrine (OMT), a quinolizidine alkaloid derived from the traditional Chinese herb Sophora Flavescens Ait, is recognized for its extensive pharmacological properties, including anti-inflammatory, antioxidant, antiviral, immunoregulatory activities, and its antitumor effects on various solid tumors. This study extends the investigation of OMT to its potential impact on human multiple myeloma (MM), with a novel emphasis on its implications for mental health and physical fitness in athletes undergoing cancer treatment. Materials and Methods: In this study, MM cell lines MMU266, ARP-1, and RPMI8226 were treated with varying concentrations of OMT. Assessments of cell proliferation, apoptosis, cell-cycle progression, and related signaling molecules were conducted using MTT assays, flow cytometry, Western blotting, and RT-PCR. Additionally, considerations for the impact of OMT on mental health and physical fitness were theoretically evaluated based on its pharmacological profile and potential influence on systemic health. Results: OMT treatment significantly inhibited MM cell proliferation, induced G0/G1 phase cell cycle arrest, and promoted apoptosis, accompanied by downregulation of HIAP-1, HIAP-2, Bcl-2, and Survivin. The mechanisms underlying these effects include the inhibition of the PI3K-Akt-mTOR signaling pathway and the activation of caspase-dependent apoptosis pathways. Significantly, OMT also inhibited the proliferation of primary MM cells isolated from patient bone marrow samples. Theoretical considerations suggest that OMT's anti-inflammatory and immunoregulatory properties may offer additional benefits for mental health and physical fitness in athletes, potentially aiding in the management of stress, improving resilience, and supporting overall well-being during cancer treatment. Conclusion: Our findings indicate that OMT not only exhibits potent anti-myeloma activity through cell cycle arrest, PI3K-Akt-mTOR pathway inhibition, and caspase-dependent apoptosis but also holds promise for supporting mental health and physical fitness in athletes with MM. These multifaceted benefits position OMT as a promising candidate for both the treatment of MM and the enhancement of quality of life for athletes undergoing cancer therapy.