Background: Pyroptosis, a highly inflammatory form of programmed cell death, plays a key role in diseases such as sepsis, rheumatoid arthritis, Alzheimer’s disease, and COPD. It is driven by inflammasome activation, leading to the release of pro-inflammatory cytokines. Pyridoxine (Vitamin B6), an essential micronutrient with known anti-inflammatory effects, has been suggested as a potential regulator of inflammasome activation and pyroptosis. This review examines current evidence on pyridoxine’s role in modulating pyroptosis. Methods: A literature search was conducted in PubMed, Scopus, and Web of Science for studies published between 2014 and 2024. The search focused on pyridoxine’s relationship with inflammation, inflammasomes, and pyroptosis pathways using keywords such as “pyridoxine,” “Vitamin B6,” “pyroptosis,” “inflammasome,” “caspase-1,” and “gasdermin D.” Both preclinical and human studies were reviewed, with emphasis on molecular mechanisms underlying pyridoxine’s anti-inflammatory effects. Results: Studies consistently showed that pyridoxine reduced inflammasome activation, decreased pro-inflammatory cytokine production, and inhibited caspase-1 (CASP-1) activity, thereby suppressing pyroptosis. Human studies, though indirect, linked higher pyridoxine levels to reduced systemic inflammation, suggesting a possible anti-pyroptotic effect. Conclusions: Pyridoxine shows potential as an anti-pyroptotic agent due to its anti-inflammatory and immunomodulatory properties. However, further well-designed clinical trials are needed to confirm its role in controlling pyroptosis, especially in diseases associated with excessive inflammasome activation. © The Author(s), under exclusive licence to Springer Nature Switzerland AG 2025.