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With the increase in verifications and proofs highlighting the association between diet and health, several food products, such as phenolic rich fruits and vegetables, have emerged as possessing potential health benefits. Plants rich with fiber and phenolic content have long been considered as a health-promoting dietary intervention. Therefore, the present work aimed to test the independent and combined potential benefits of mangosteen pericarp extract (MPE) and curcuma rhizome extract (CRE) consumption through an in vivo study on Wister albino rats. The data demonstrated that the three nutritional interventions had no effect on serotonin or glutamate, but dopamine was considerably increased in response to the combined effects of MPE and curcuma (p ˂ 0.025). The anti-inflammatory potency of independent MPE and curcuma, as well as their combined effects, recorded lower levels of IL12 in all groups compared to controls (p ˂ 0.05), and only a considerably lower IL-6 in combination treatment only (p ˂ 0.028). The three dietary interventions dramatically lowered leptin levels, with the combined treatment significantly lower than the healthy control group (p ˂ 0.001). The combined treatment significantly improved levels of malondialdehyde (MDA) and GSH as indicators of oxidative stress and antioxidant capability. Our data reported anti-dyslipidemic and anti-hyperglycemic effects of the three studied nutritional interventions, with the independent curcuma being the most effective anti-hyperglycemic compound (p ˂ 0.009). Collectively, the three used nutritional intervention strategies demonstrated promising health-promoting effects with no side effects. Full article