Molecular validation confirmed that R-S downregulated the mRNA expression of IL-1β, IL-6, TNF-α, MAPK 14, MAPK 8, NFKB 1, FOS, and JUN, and suppressed the phosphorylation of p38 MAPK, JNK, and NF-κB p65.<h4>Conclusion</h4>The R-S combination alleviates cisplatin-induced AKI by modulating the gut microbiota, regulating metabolic profiles, and suppressing the MAPK signaling axis. Here, IL6 is linked to acute kidney injury.