Diabetes mellitus (DM) and its associated complications are metabolic disorders characterized by hyperglycemia, leading to high morbidity and reduced quality of life worldwide. This global healthcare problem imposes substantial personal and social burdens that warrant comprehensive and in-depth investigation. Plantamajoside (PMS), a naturally bioactive ingredient derived from the traditional Chinese medicinal herb , exhibits a range of pharmacological properties, including anti-inflammatory, antioxidative, and antitumor effects, and has been traditionally utilized in clinical applications such as removing phlegm and clearing heat. However, the potential biological impact of PMS on DM remains largely unexplored. Recent research by Wang reported the therapeutic potential of PMS in type 2 DM (T2DM) and elucidated the underlying molecular mechanisms. Specifically, PMS mitigates endoplasmic reticulum stress and apoptosis of pancreatic β-cells by upregulating DnaJ heat shock protein family (Hsp40) member C1, thereby alleviating pancreatic β-cell damage and ameliorating T2DM progression. Given the novel and protective effect of PMS on pancreatic β-cells, this natural ingredient emerges as an innovative and promising therapeutic strategy for improving DM outcomes. PMS has been shown to modulate key signaling pathways involved in multiple types of regulated cell death (RCD), such as apoptosis and autophagy. Various forms of RCD, including apoptosis, ferroptosis, pyroptosis, autophagy, and PANoptosis, contribute to the pathogenesis of DM and its associated complications. There is significant potential for PMS to exert protective effects on β-cells against these forms of RCD and to provide a multitarget approach to DM therapy. Therefore, further exploration into whether PMS shields pancreatic β-cells from these types of RCD, coupled with elucidating the underlying molecular mechanisms, will facilitate the development of more effective therapeutic strategies for DM. Additionally, further investigation on PMS in conjunction with other therapeutic approaches is warranted to enhance therapeutic efficacy for DM.