<p>Parkinson’s disease (PD) is an advanced neurodegenerative condition distinguished by the rapid decline of dopamine neurons in the midbrain, leading to an imbalance in dopamine and acetylcholine levels, precipitating associated symptoms. The main objective of this work was to fabricate solid lipid nanoparticles (SLNs) loaded with S-carboxymethyl-L-cystine (SC) for enhanced delivery to the brain. This study examines the impact of these SLNs on rotenone (RT) caused Parkinson’s disease (PD) in both rat and zebrafish models. The process of loading SC into SLNs was achieved through the solvent evaporation-emulsification method. The SC-encapsulated solid lipid nanoparticles (SCSLNs) were subjected to physicochemical evaluation, and their properties were verified. For 28 days, the rats received subcutaneous injections of RT at a dosage of 2&#xa0;mg × kg⁻¹ body weight. Additionally, the rats in the experimental group received SCSLNs from the 14th to the 28th days of the trial. Interestingly, the locomotor activity, grip strength, and exploratory behaviour of the rats with SCSLNs significantly improved. Furthermore, it was observed that the quantities of acetylcholinesterase (AchE) inside the brain tissue had increased, and oxidative biomarkers had decreased. In addition, there was a discernible decrease in Lewy body development and cellular damage compared to the positive control group. Zebrafish were dosed with SCSLNs simultaneously as they were subjected to a 5&#xa0;µg × L⁻¹ RT concentration for 28 days during the experiment. AchE levels in the fish brain increased, resulting in improved locomotor activity in the SCSLN group of zebrafish. The findings of this investigation imply that using SCSLNs may reduce Parkinson’s disease symptoms via enhanced delivery of SC into the brain.</p>