Purpose <p>This study evaluates the potential of ramie (<i>Boehmeria nivea L. Gaud</i>) and mango seed kernel (<i>Mangifera indica L.</i>) and their combination in reducing methane emission, modifying rumen fermentation, and influencing ruminal enzymes activity under <i>in-vitro</i> conditions.</p> Methods <p>A total mixed ration (TMR) consisting of 40% berseem, 20% wheat straw, and 40% concentrate was used as the control. In the treatment groups, berseem was replaced with ramie at 10%, 20%, 30%, 40%, and 50%. In another trial, mango seed kernel (MSK) was incorporated into the TMR at 1%, 3%, 5%, 7%, and 10% levels. Based on dry matter degradability and methane reduction, the two most effective levels of ramie (40% and 50%) were selected and combined with MSK at different inclusion rates (1%, 3%, 5%, 7%, and 10%) for further evaluation.</p> Results <p>The combination of 50% ramie with 5% MSK reduced methane emissions by 36.02% without significantly (<i>P</i> &gt; 0.05) affecting in vitro dry matter and organic matter degradability. Higher levels of MSK significantly (<i>P</i> &lt; 0.05) reduced ammonia nitrogen (NH3-N) concentration and acetic acid production while significantly (<i>P</i> &lt; 0.05) increasing propionic acid levels. However, a significant (P &lt; 0.05) reduction in fiber digestion was observed at higher inclusion levels.</p> Conclusion <p>The inclusion of ramie and MSK in the diet effectively mitigates methane emissions while maintaining fermentation efficiency at moderate levels of supplementation (50% ramie + 5% MSK). Further <i>in-vivo</i> research is needed to validate its impact on animal performance and productivity.</p> Graphical Abstract <p></p>