This study investigates the cytotoxic and biochemical effects of PEGylated graphene oxide sol-gel (SJ-go) nanoparticles, curcumin, and quercetin on BEAS-2B human bronchial epithelial. In this work, a new graphene oxide nanocomposite (SJ-go) was produced using the sol-gel method through a one-step reaction. These hybrid sol-gel systems include graphite, triethyl orthosilicate (TEOS), and polyethylene glycol (PEG) having a molecular weight of 8000 g/mol. IC50 value for SJ-go was found to be 318.86 μg/mL. While IC50 value of curcumin was 28.99 μM, it was 169.40 μM. SJ-go at 150 μg/mL decreased the Glutathione Peroxidase (GSH-Px) activity from 32.14 ± 1.51 U/mg to 4.18 ± 0.02 U/mg protein when compared with positive control without nanoparticles. Data showed the SJ-go at the highest concentration was more effective on GSH-Px in terms of cytotoxic when compared with SJ-go, itself without treatment with any substances for antioxidant mechanism. When considering natural substances, the curcumin was also more effective than the quercetin on SJ-go treated BEAS-2B at all concentrations of the sol-gel graphene oxide in terms of GSH-Px levels below and above IC50 value. Interleukin-6 (IL-6) analysis indicated that the curcumin has more anti-inflammatory effect than quercetin at all nanoparticles’ concentrations.