The gut microbiome supports immune health and influences gut and heart functions through the gut-heart axis. Synbiotics (SBT), combining probiotics and prebiotics, help restore microbiome balance. Chemotherapy often disrupts this balance, leading to adverse effects on the gut and heart. This study explores the potential of SBT supplementation in reducing heart and gut inflammation caused by doxorubicin (DOX) chemotherapy. The gut microbiome plays a vital role in immune health, and metabolites produced by gut bacteria contribute to physiological functions through the gut-heart axis. Chemotherapy drugs often disrupt these processes, leading to adverse effects on internal organs. Using 24 ICR male mice divided into four groups, the experiment assessed the impact of SBT on DOX-induced damage. Results indicated that DOX treatment significantly worsened survival rates, physical performance, heart function, and gut microbiome stability. However, co-treatment with SBT improved these markers, suggesting that SBT may help mitigate chemotherapy-induced side effects in cancer patients.