Background: Arsenic (As) contributes to metabolic disorders, including diabetes, and disrupts the functions of multiple systems, leading to associated diseases and dysfunctions. This study aims to investigate the effects of Arsenic on plasma and liver enzymes, assess liver tissue histopathological changes, and explore spirulina's potential protective role against As-induced liver damage. Materials and Methods: Female Wistar rats were divided into six groups, including control, sodium arsenate-only (5mg/kg body weight), Sp-only (300mg and 600mg), and combined As and Sp treatment groups. Plasma and liver samples were collected after four weeks of treatment for enzyme analysis, and part of the liver tissues were examined histologically. Results: Arsenic exposure significantly increased aspartate aminotransferase (AST), alanine transaminase (ALT), alkaline phosphatase (ALP), and lactate dehydrogenase (LDH) enzyme levels in plasma and liver. However, Sp supplementation at different doses showed a reduction in enzyme levels, although not statistically significant. Histological examination revealed liver damage in the As-exposed group, including congestion, leukocyte infiltration, and endothelium detachment. Sp supplementation partially attenuated these changes. Conclusion: This study enhances understanding of As's toxic effects and suggests that Sp supplementation may offer some protection against As-induced liver damage. Recommendation: To improve the findings, additional parameters such as oxidative stress markers, inflammatory markers, and liver function tests should be incorporated. These measurements will provide a more comprehensive understanding of the effects of arsenate exposure.