As part of a series of experiments in our laboratory, we studied the effect of fluoride (F) alone or with buffalo (Bubalus bubalis) pineal proteins (BPP) and melatonin (MEL) on certain plasma biochemical parameters in rats. Six groups of six adult female Wistar rats weighing 123-142 g with an untreated group as Control were administered BPP (100 ?g/kg BW, i.p.), MEL (10 mg/kg bw, i.p.), F (from NaF at 150 ppm F ion in their drinking water), F+BPP, and F+MEL daily for 28 days. Blood samples were collected at the end of the experiment to estimate plasma glucose, proteins, sodium (Na+), potassium (K+), urea, creatinine, cholesterol, blood urea nitrogen (BUN), serum glutamate pyruvate transaminase (SGPT), serum glutamate oxaloacetate transaminase (SGOT), and alkaline phosphatase (ALP) activity. There was no significant variation in glucose, protein, and K+ level among the Control, BPP, and MEL groups. However, significantly (p<0.05) higher levels of plasma glucose were observed in the F+BPP and F+MEL-treated rats. Plasma creatinine, urea, BUN, cholesterol, K+, and Na+ concentrations and also SGPT, SGOT, and ALP activities were significantly higher (p<0.05) in the F-treated animals as compared to the Control group. Administration of BPP and MEL in F-treated rats caused significant (p<0.05) reduction of these adverse changes. BPP and MEL alone resulted in significant (p<0.05) increase in plasma Na+, ALP, and cholesterol. These findings clearly indicated that BPP and MEL had significant ameliorative effects on adverse F- induced changes in certain biochemical parameters in rats. Since they also exhibited no evidence of deleterious alterations in biochemical profiles, BPP and MEL can be considered suitable for testing their beneficial effects on F toxicity in humans.