The abundance of nanoplastics (NPs) in marine ecosystems has raised significant concerns about their potential ecotoxicological effects, primarily on sessile bivalves. The present evaluation aimed to assess the toxico-transcriptomic impact of polystyrene nanoplastics (PS-NPs) on the intertidal clam, Gafrarium divaricatum. The clams were subjected to PS-NPs (10 mg/L) for 96 h, and the gill tissues were collected for transcriptomic and histopathological analyses. The de novo transcriptome assembly, performed using Trinity, generated 661,554 unigenes with a BUSCO completeness of 98.8%, establishing a high-quality genomic resource for this species. Differential gene expression analysis identified 1,182 upregulated and 1,626 downregulated transcripts, with major functional categories related to immune modulation, antioxidant defence, apoptosis, and cellular architectural changes, that are broadly consistent with NP-induced responses previously documented in other bivalves. Gene ontology enrichment analysis revealed involvement of genes in important molecular activities like transporter and catalytic activity, as well as biological processes like protein folding and mitochondrial metabolism. The q-PCR analysis of selected transcripts further confirmed the consistency of the expression pattern in line with RNA-Seq data. The histopathological examination revealed marked structural alterations in gill tissues, including ciliary erosion, lamellae fusion, and lipofuscin granular accumulation, supplementing the transcriptomic findings of tissue-level toxicity. These molecular responses corroborate with established NP-related stress patterns in bivalves. This study represents the first transcriptome resource for this species and provides greater insights into the molecular mechanisms underlying NP toxicity in marine bivalves, contributing to broader efforts for developing suitable strategies for conservation of marine biodiversity.