Protective Strategies Against Glyphosate and Glyphosate-Based Herbicide Toxicity: Mechanisms, Experimental Evidence, and Translational Limitations.

(1) Background: Glyphosate (GLY) and glyphosate-based herbicides (GBHs) are widely used agrochemicals. Experimental studies have reported oxidative stress, inflammatory activation, mitochondrial impairment, endocrine-related effects, and organ injury following GLY/GBH exposure; however, candidate mitigation approaches have not been comprehensively summarized across experimental systems. (2) Methods: This structured narrative review followed SANRA recommendations. PubMed, Scopus, Web of Science, and Embase were searched (January 2004-January 2026). In total, 37 experimental studies met the inclusion criteria, describing 23 compounds categorized as vitamins, antioxidants, or enzyme modulators, dietary supplements, plant extracts, humic substances, hormonal modulators, and other natural compounds. (3) Results: Across models, reported protective effects most consistently involved attenuation of oxidative damage, including reductions in lipid peroxidation, oxidative DNA damage markers, and partial restoration of endogenous antioxidant defenses. Several interventions also modulated inflammatory signaling, apoptosis-associated markers, and stress response signaling. Protective effects were generally dose-dependent and more frequently observed in pre-treatment or co-exposure paradigms; complete normalization of outcomes was uncommon. Interpretation across studies was limited by heterogeneity in exposure conditions, test systems, endpoints, and, critically, by differences between pure GLY and GBHs. (4) Conclusions: Experimental evidence supports the mechanistic plausibility of antioxidant and stress response modulation as candidate approaches to mitigate GLY/GBH-induced toxicity. However, substantial methodological variability, frequent use of high-dose or non-representative exposure paradigms, and the absence of human interventional data limit translational relevance. Future studies should prioritize standardized, formulation-specific designs with exposure scenarios aligned to real-world conditions and include systematic safety assessment of proposed interventions.