The current study aimed to show the seasonal fluctuations' impact on the composition and bioactivities of the essential oil (EO) of Zanthoxylum piperitum (L.) DC. 'Odorum' (the Odorum) leaves. The four seasons steam-distilled EOs were examined chemically using GC/MS, followed by molecular networking, and tested biologically for antioxidant and an-timicrobial characteristics. The identified compounds (47) were molecularly docked against 11 antimicrobial targets. The highest yield was obtained in Winter (0.552 %). GC/MS analysis displayed monoterpenes, sesquiterpenes, and cin-namic acid derivatives as the major chemical classes in all seasons. Winter EO had the highest D-limonene level (66.37 %), and the strongest significant (p<0.05) antioxidant action in the assays of FRAP (41.81 ± 4.63 μM Trolox equivalent/ mg EO) and ORAC (438.00 ± 23.24 μM Trolox equivalent/ mg EO). E-methyl cinnamate predominated in EOs of sum-mer (47.78%) and fall (45.91%). Each season exhibited a predominant bactericidal/fungicidal effect against certain GIT pathogens; Summer EO had the most potent action against Bacillus subtilis (MIC and MBC= 1.97 µg/ml), Enterococcus faecalis (MIC and MBC = 125 µg/ml), Escherichia coli (MIC and MBC= 15.6 µg/ml), and Candida albicans (MIC = 1.97 µg/ml) and (MBC=3.9 µg/ml); while fall EO was the most powerful against Salmonella typhimurium (MIC= 1.97 µg/ml) and (MBC=3.9 µg/ml); whereas winter EO showed the utmost activity against Helicobacter pylori (MIC = 3.9 µg/ml) and (MBC =.7.8 µg/ml). Docking studies clarified 10 compounds with superior affinity than that of the native co-crystallized ligands mainly towards 3 target proteins. Hence, The Odorum EO could be strongly regarded as a prom-ising natural food preservative.