Multiple sclerosis is characterized by the demyelination of neurons, which is a chronic inflammatory disease of the central nervous system. This autoimmune disorder occurs due to an imbalance in the body's immune system as a result of uncontrolled oxidative stress. The B and T lymphocytes cross the blood-brain barrier and destroy the myelin sheath. Multiple sclerosis is one of the most common causes of disability in young adults affecting approximately 3 million individuals worldwide. Among them, females are considered at higher risk than males. It disrupts the normal functioning of life badly and major symptoms include loss of sensation, poor vision, impaired hearing, and cognitive abnormalities. Several treatments and drugs have been used to treat this medical condition, but they pose serious side effects also. So, the need of the hour is to explore such natural bioactive compounds that have neuroprotective properties, thus leading to the treatment of neurodegenerative disorders. Among various plants with medicinal properties, Gerbera jamesonii is a plant that exhibits antioxidant, anti-inflammatory, and neuroprotective properties. To enhance its therapeutic potential, this study aimed to load its ethanolic extract into solid-lipid nanoparticle formulations (SLNs), which is an innovative approach for treatment because nanoparticles provide effective targeted drug delivery due to their extremely small size. Solid-lipid nanoparticles were prepared using the emulsification-solvent evaporation method. For experimental design, 30 Wistar rats were randomly divided into seven groups (n = 10): normal, demyelination disease model, standard drugs, dimethyl fumarate and fingolimod (FTY 720) 15 mg/kg, and three treatment groups: GJ-NPs 250 mg/kg, 500 mg/kg, and 750 mg/kg. Prior to treatment, 0.2% cuprizone solution was prepared for the induction of multiple sclerosis in all groups except the normal group for 42 days. Biochemical analyses such as determination of inflammatory biomarkers and antioxidant enzymes were performed. The plant extract was subjected to HPLC to examine its phenolic compounds which are active in healing neurodegeneration. Physiological changes in rats were observed such as motor dysfunction and anxiety-like behavior caused by cuprizone. Behavioral tests showed significant improvement of motor function, muscular coordination, and enhanced cognitive abilities in the treatment groups as compared to the demyelination disease model. Histopathology of the rat brain regions showed significant differences in the normal and demyelinated areas. The results showed that GJ-NPs treated demyelination, modulating oxidative stress manifested by pro-inflammatory cytokines TNF-α, IL-6, AβPP, α-synuclein, NF-B, etc., thus restoring the levels of antioxidant enzymes to normal range.