<p>Chronic renal impairment can be caused by prolonged exposure to lithium (Li), which is considered a prototype medication for the treatment of bipolar disorders (BDs). The current study aimed to enhance the biological efficacy of biosynthesized gold nanoparticles (Au-NPs) using an algal extract from <i>Nannochloropsis oculata</i> to mitigate the neurotoxicity and kidney damage induced by Li in rats. The kidney and brain tissues were analyzed using conventional biochemical tests to assess oxidative stress and inflammatory responses. Electrophoretic techniques were used to examine native protein and isoenzyme patterns. Histopathological analysis was conducted on both tissues. mRNA expression levels of inflammatory markers (NF-κB, IL-6, and IL-1β) and antioxidant enzymes (SOD1, CAT, and GPx1) were also measured. The study found that the gold <i>N. oculata</i> nano-extract restored normal hematological and biochemical parameters that were affected by an injection of lithium carbonate (Li₂CO₃). It improved antioxidant indicators, reduced inflammatory markers, and enhanced the antioxidant state of kidney and brain tissues. The gold nano-extract also reduced histopathological damage to the brain and kidney caused by Li₂CO₃. Furthermore, it alleviated the differences in electrophoretic patterns between the Li₂CO₃-injected group and the control group. The nano-extract also restored mRNA expression of inflammatory markers and antioxidant enzymes that were altered by Li₂CO₃ intoxication. The study found that the gold <i>N. oculata</i> nano-extract reduced kidney and brain toxicity at various levels, including biochemical, histopathological, physiological, and molecular.</p>