Understanding how soil organic matter (SOM) responds to agricultural management at the molecular scale remains a central challenge, particularly in semi-arid Mediterranean systems where long-term monitoring is limited, and soils face marked seasonal fluctuations, salinity constraints, and sustained cultivation pressure. In this study, lignin and lipid biomarkers were combined to provide complementary views of SOM dynamics in the agricultural soils of Oued Rhiou (Algeria), enabling the simultaneous assessment of plant-derived inputs, microbial processing, and stabilization pathways under cultivation and subsequent rest periods. Depth-dependent patterns showed that lignin indicators responded strongly to shifts between crop residue inputs and root-derived material, while lipid proxies captured changes in microbial activity, biosynthesis, and OM stabilization. Surface soils exhibited enhanced microbial turnover during cultivation, whereas deeper layers were characterized by selective preservation of recalcitrant compounds. Principal Component Analysis (PCA) further highlighted these processes by distinguishing vegetation-driven variability from microbial reworking patterns, with subset analyses (lignin-only and lipid-only) providing clearer explanatory power than the combined dataset. Collectively, the findings underscore the importance of integrating rest periods into agricultural cycles to promote SOM stabilization, highlight the complementarity of lignin and lipid proxies for deciphering SOM transformation pathways, and offer molecular-level insights that can guide sustainable soil management strategies aimed at balancing productivity, soil resilience, and long-term carbon sequestration.