Follicular atresia is mainly driven by the oxidative stress-induced apoptosis of granulosa cells (GCs). Oxidative stress mediated by H2O2 is the predominant form of stress in cells and plays a key role in the death of porcine GCs. In the present study, using integrated transcriptomic and untargeted metabolomic approaches, we explored the mechanisms underlying the regulation of oxidative stress in porcine follicular GCs. Per the transcriptomic analysis, compared with the control group, we identified 328 differentially expressed mRNAs (260 upregulated, 68 downregulated) in the H2O2-treatment group; these mRNAs were significantly enriched in apoptosis-related pathways, including the tumour necrosis factor (TNF) and p53 signalling pathways. Furthermore, via untargeted metabolomic analysis, we identified 150 differentially expressed metabolites (101 positive, 49 negative). The pathways associated with protein digestion and absorption, glycine, serine, and threonine metabolism, amino acid biosynthesis, and carbon metabolism were enriched with these metabolites. The integrated transcriptomic and metabolomic analyses revealed taurine, creatine, L-serine, and hypoxanthine as the key metabolites under H2O2-induced oxidative stress. Both the differential genes and metabolites were notably enriched in the FOXO and mineral absorption pathways. In the present study, we elucidated the regulatory mechanism underlying H2O2-induced oxidative stress in porcine follicular GCs via transcriptomic and metabolomic analyses. Our findings offer novel insights into the alleviation of oxidative stress in GCs.