Background and Objectives: Neuroinflammation is linked with numerous neurodegenerative illnesses, which includes amyotrophic lateral sclerosis (ALS). In this study, we investigate the anti-inflammatory, anti-oxidant, and anti-apoptotic properties of two non-psychoactive phytocannabinoids, cannabigerol (CBG) and cannabidiol (CBD). Supplies and Solutions: The motoneuron-like cell line NSC-34 differentiated by serum deprivation and with the more therapy of all-trans retinoic acid (RA) is a valid model to investigate molecular events linked to neurodegeneration in ALS. Benefits: Pre-therapy with CBG (at two.five and five µM doses) alone and in mixture with CBD (at two.five and five µM doses) was in a position to lessen neuroinflammation induced by a culture medium of LPS-stimulated macrophages. In certain, the pre-therapy with CBD at a five µM dose decreased TNF-α levels and enhanced IL10 and IL-37 expression. CBG-CBD association at a five µM dose also decreased NF-kB nuclear element activation with low degradation of the inhibitor of kappaB alpha (IkBα). CBG and CBD co-administered at a five µM dose decreased iNOS expression and enhanced Nrf2 levels. Additionally, the pre-therapy with the association of two non-psychoactive cannabinoids downregulated Bax protein expression and upregulated Bcl-two expression. Our information show the anti-inflammatory, anti-oxidant, and anti-apoptotic effects PPARγ-mediated. Conclusions: Our final results give preliminary assistance on the prospective therapeutic application of a CBG-CBD mixture for additional preclinical research.