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Environmental accumulation of fluoride poses a significant public health challenge globally, with syndrome of fluorosis affecting both humans and livestock through skeletal deformities, dental lesions, metabolic disruption and oxidative stress. Most studies are primarily carried on its impact on mankind. Limited studies on impact of fluoride exposure on livestock are available and none from the study region. Cattle calves are considered as ideal bio-indicators for fluoridated drinking water. We estimated impact of fluoride exposure in cattle population and investigated to analyze the therapeutic efficacy of Spirulina platensis (SP) in mitigating fluorosis in cattle calves. A total of 20 stall-fed calves were randomly and equally divided into one disease control (II) group, two test (III-IV) groups and one reference treatment group V. They were compared with group 1 as baseline healthy control. The study was suggestive of ameliorative potential of SP provided to test groups III and IV calves based on significant improvements in hemato-biochemical and oxidant-antioxidant profiles. Notably, SP at 650 mg/kg body weight per day supplementation in group IV significantly lowered serum and urinary fluoride levels comparable to reference treatment group V calves. These findings underscore the potential of drinking water SP as a sustainable, nutrient-rich intervention for managing livestock reared in endemic areas with fluoride-contaminated groundwater.