Estimating the period since death is forensic medicine's primary priority. It assists other judicial inquiries in comprehending the situation and accounting for prospective offenders. Objectives: The current research is attempting to evaluate the role of various methods in the estimation of the postmortem interval by studying the biochemical changes in the blood (serum levels of uric acid, lactate, amylase, lipase, and insulin), histological changes, and anti-p53 antibody immunohistochemical expression in the tongue and pancreas. Methodology: Forty adult male Albino rats served as the subjects for the current investigation. According to varied postmortem intervals, the animals were randomly divided into four groups: 0 hours, 12 hours, 24 hours, and 48 hours after death. Results: The postmortem interval, serum uric acid, lactate, and lipase displayed a significant positive correlation. Time-dependent alterations could be observed in the pancreatic and tongue histological sections. Anti-p53 antibody immunohistochemistry expression increased progressively over the postmortem period. Conclusions: Determining how long has transpired after death is essential in forensic medicine. The serum lactate level is the most accurate of the studied biochemical parameters. Additionally, regression formulas using the optical density scores of the tongue and pancreas can be used to forecast PMI more accurately when combined.