Plastic pollution is a global challenge and has emerged as a concerning environmental and public health issue. While the harmful effects of macro plastics are well-known, recent attention has shifted towards smaller microplastics (MPs) and nanoplastic (NPs), which have been reported affect marine and terrestrial organism. Although various studies have highlighted the liver as a potential target organ, the effects of these particles on mammalian liver health remain underexplored. To address this knowledge gap, our study focuses on hepatoxic effects of polystyrene micro- (PS-MPs) nanoplastics (PS-NPs) specifically on adult male Swiss albino mice. To understand the accumulation and histopathological impacts on the liver, mice were orally administered fluorescent PS-MPs (size 2 μm) for 8-week duration. Additionally, to assess the hepatotoxic effects of smaller size particles, mice were orally administered PS-NPs (size 50 nm) for the same 8-week period. Furthermore, we also compared the effects of PS-MPs and PS-NPs on stress levels by estimating plasma cortisol level of the treated mice. Our results showed that PS-MPs after accumulating in the liver and induced notable histopathological changes. On the other hand, exposure to smaller sized PS-NPs led to oxidative stress, evident by alterations in levels of CAT, SOD, GSH and LPO in the liver. Interestingly, exposure to both PS-MPs and PS-NPs resulted in an elevation of cortisol levels in the blood plasma of the exposed mice. These findings highlight the potential risks associated with plastic particles of various sizes, as both PS-MPs and PS-NPs demonstrate harmful impacts on liver function and stress hormone regulation.