Nanoparticles (NPs) have actively contributed to nanotechnologies advancement over the last years, due to the unique properties they possess compared to their pristine counterparts. Consequently, NPs found wide applications in various fields such as the medical, biomedical, chemical, agro-food industries, and cosmetology. NP's extensive uses could lead to their release into the environment, especially in the marine ecosystems, considered as NPs sink, resulting in harmful effects on organisms. Concerns regarding NPs' toxicity in aquatic organisms have emerged, however, several points remain unexplored. In the present study, the toxicity of chromium oxide (Cr2O3 = 42 nm) and aluminum oxide (Al2O3 = 38 nm) NPs (1 mg/L, 2.5 mg/L, and 5 mg/L) in the gills of the marine gastropod Stramonita haemastoma was assessed through time (7, 14, and 28 days) by a multi-biomarker, Integrated biomarkers response (IBR), and Histological analysis. Both NPs induced varied changes in the antioxidant system, suggesting the onset of oxidative stress marked by superoxide dismutase (SOD), catalase (CAT), acetylcholinesterase (AChE), metallothionein (MT), and malondialdehyde (MDA) levels imbalance. Varied histological alterations in the gills of S. haemastoma were also observed including inflammation, hypertrophy, and lamellar fusion, IBR proved to be a promising tool for assessing NPs toxicity in gastropods. In this study results indicated the co-response of reduced glutathione (GSH), glutathione S-transferase (GST), glutathione peroxidase (GPx), CAT, SOD, and MT after 28 days of exposure. S. haemastoma showed sensitivity to all exposure concentrations of NPs thus validating this species as a suitable indicator of NPs contamination and toxicity.