Although studies have shown that ginger, as an herbal remedy and zinc are able to improve inflammation, oxidative stress, autophagy, and metabolism of lipid and glucose, their molecular mechanisms are unknown. Therefore, this study was aimed to examine the therapeutic effects of ginger with zinc supplement for eight weeks on fructose-induced metabolic syndrome (MS). Ninety-six adult male Sprague Dawley rats (220 g ± 20) were randomly assigned to twelve controlled and treated groups. After the last treatment session, the level of lipid profiles, glucose, insulin, and leptin as metabolic factors and liver enzymes as biomarkers to evaluate liver function in serum were measured. The level of antioxidant enzymes and lipid peroxidation to evaluate the oxidative status and the TNF-α level as a biomarker to assess the state of inflammation in liver were also measured. The level of zinc along with the expression of NF-κB, mTORC1, PPAR-α, SREBP-1c, and Nrf2 in liver was also evaluated. The level of metabolic factors and liver enzymes in serum along with lipid peroxidation and TNF-α in liver increased; zinc and antioxidant enzymes levels decreased in rats with MS compared to control rats (p < .05). The hepatic expression of SREBP-1c, NF-κB and mTORC1 were upregulated and the expression of PPAR-α and Nrf2 were downregulated in rats with MS compared to control rats (p < .05). Treatment with different doses of ginger, zinc, and the combination of them could improve metabolic, inflammatory oxidative stress factors, and expression of the above genes in rats with MS compared to the MS group (p < .05). It can be concluded that ginger, zinc, and the combination of them could improve oxidative damage, inflammation, and autophagy induced by fructose and could adjust the glucose and lipid metabolism and the homeostasis of zinc in rats with MS. PRACTICAL APPLICATIONS: Due to the increasing prevalence of metabolic diseases, the use of plant compounds such as ginger has attracted widespread attention. Ginger as an herbal remedy with predominant pharmacological properties due to its availability, cheapness, and lack of side effects is also very popular for the treatment of metabolic disorders in folk medicine. Moreover, enhancing its medicinal properties with supplements such as zinc can be widely welcomed. This study was actually performed with the aim of investigating the effects of ginger + zinc supplement on MS. The results showed that the ginger + zinc supplement could improve oxidative damage, inflammation, and autophagy caused by fructose and adjust the glucose and lipid metabolism and the homeostasis of zinc in rats with MS. The results of this study support the hypothesis that ginger can be used as a very suitable option for the production of medicinal supplements to maintain human health.