Background: Pesticide exposure and Helicobacter pylori infection are two common environmental risk factors. Egyptian farmers often face the dual challenge of both. However, the synergistic effects of these two factors remain poorly understood. Objective: To investigate effects of pesticide exposure and Helicobacter pylori infection on biochemical parameters. Subjects and Methods: 86 farmers chronically exposed to pesticides along with 64 matched unexposed controls were enrolled, the two groups were subdivided based on Helicobacter pylori infection into 4 subgroups: group A (unexposed/uninfected, n=32), group B (unexposed/infected n=32), group C (exposed/uninfected, n=33), and group D (exposed/infected (n=53). Biochemical and oxidative markers were measured, as well as exposure and infection markers.  Statistical analyses: The statistics were performed with the SPSS (version 27) program. Results: Malondialdehyde levels showed a significant step-by-step increase in groups B, C, and D compared to group A. Glutathione-s-transferase activity decreased in exposed groups (C and D) compared to non-exposed controls (A). The activities of Butyrylcholinesterase showed significant reduction in the exposed groups (C and D) compared to the non-exposed groups (A and B). Creatinine was significantly higher in the C and D exposed groups compared to the A group, and the level of calcium, magnesium, and iron was also gradually decreased from control to the exposed/infected group. However, prevalence of Helicobacter pylori and liver enzymes are comparable between groups. Conclusion: Pesticide exposure and Helicobacter pylori infection synergistically disturbed the studied biomarkers in Egyptian farmers, revealing amplified biochemical impacts from the combined exposures versus individually.