Caenorhabditis elegans (C. elegans), a free-living nematode has been widely applied for numerous disease research. In this study, we employed C. elegans as the in vivo animal model to determine the protective effects of food bioactives on obesity and aging, as well as examine the potential effect of environmental pollutants on reproductive health. trans-Trismethoxy resveratrol (TMR) is a methyl analog of resveratrol, found to exhibit enhanced biological effects over resveratrol. However, its role in lipid metabolism is not fully understood. Our results showed that TMR significantly reduced fat accumulation in C. elegans, without affecting nematode growth, food intake, and reproduction. The fat reduction effect of TMR was dependent on the stearoyl-CoA desaturase genes fat-6 and fat-7. p-Coumaric acid, a hydroxycinnamic acid presents in peanuts, carrots, and garlic, exerts many biological properties. We found that p-coumaric acid significantly reduced the intercellular reactive oxygen species levels and increased the worms’ survival under oxidative and osmosis stressed conditions. The increased oxidative resistance induced by p-coumaric acid was found to be mediated by skn-1, an ortholog of the Nrf2 transcriptional factor and enhanced osmosis resistance may due to the downregulation of osmosis regulatory gene osr-1. PFBS, a shorter chain PFAS cognate of PFOS, has been used as a safer alternative of PFOS. However, emerging evidences suggest the safety concern of PFBS, and its effect on reproductive health is still understudied. We reported that PFOS and PFBS significantly impaired the reproduction capacity of C. elegans. Additionally, the preconception exposure of PFOS and PFBS significantly altered the embryonic nutrient loading and composition, which further lead to abnormalities in growth rate, body size, and locomotive activity in F1 offspring. Though the effective dosages of PFBS is around 100 times higher than PFOS, the internal concentration of PFBS is still around 10 times lower than that of PFOS to produce similar effects of PFOS. The current research can provide useful insight to the future studies of food bioactives and environmental contaminants on human health.