Background Live donor liver transplantation, a widely practiced procedure, involves resecting a portion of a healthy donor's liver for transplantation. Despite advancements, it poses challenges like cardiovascular instability and electrolyte imbalances, with maintaining acid-base balance being critical. This study compares the effects of 0.9% normal saline and PlasmaLyte A® on acid-base status and postoperative liver function. Methodology This prospective observational study was conducted over one year among 40 healthy adults aged 18-60 years undergoing donor hepatectomy. Patients were alternately allocated to receive either 0.9% saline (Group 1; n = 20) or PlasmaLyte A® (Group 2; n = 20). Key parameters, including acid-base status, hemodynamic parameters, and postoperative liver function, were monitored at various intervals. Statistical analysis was performed using IBM SPSS Statistics for Windows, Version 25.0 (Released 2017; IBM Corp., Armonk, NY, USA), with appropriate statistical tests. A p-value <0.05 was considered statistically significant. Results The study included 40 patients, with 20 in each group. No significant differences were observed between the groups concerning age, gender, weight, hemodynamic parameters, and urine output. However, significant differences were found in acid-base parameters. Group 2 showed better preservation of acid-base balance with higher pH and HCO₃ levels. Patients in Group 1 exhibited a significant decrease in HCO₃ levels during surgery, while those in Group 2 maintained a more stable metabolic profile. Furthermore, nine patients in Group 1 required sodium bicarbonate supplementation for metabolic acidosis, compared to only three in Group 2. Postoperative liver function tests revealed no significant differences between the two groups, although a trend toward better outcomes was observed in Group 2. Conclusions PlasmaLyte A® demonstrated superior preservation of acid-base balance compared to 0.9% normal saline, with less need for bicarbonate supplementation. While liver function outcomes were similar, the balanced solution showed a trend toward better metabolic stability, suggesting it may offer safer and more effective fluid management in liver transplantation surgery.