Oxidative stress is recognized as a common pathology that affects up to half of all men infertile. Fucoxanthin possesses antioxidant activity, and several investigators have reported anti-inflammatory action. This study extracted powder of Sargassum glaucescens by acetone to obtained fucoxanthin rich-brown algae extract (FXE). The objective of this study was to evaluate the ameliorative effects of fucoxanthin extract from Sargassum glaucescens on lipopolysaccharide-induced inflammation in RAW264.7 macrophage cells and its protective effects of against Cisplatin (CP)-induced reproductive damage in hamsters. Eighty male Syrian hamsters were injected with and without CP, then daily oral gavage with various concentrations of fucoxanthin for 5 days. Treatment with FXE reduced the level of reactive oxygen species and malondialdehyde in RAW 264.7 cells and the rats’ testis as well as protective effects on mitochondrial membrane potential. The FXE administration also improved testosterone level and alpha-glucosidase activity. The sperm count also increased after treated with FXE, whereas sperm abnormality was reduced. Histopathological analysis showed that FXE successfully improved the seminiferous tubules morphology. According to these findings, fucoxanthin extract from Sargassum glaucescens can be used as an alternative for the treatment of testicular damage.