A reliable RP-HPLC analytical method with UV detection at 421 nm was developed and validated for the quantitative determination of curcumin from rat plasma after oral administration of curcumin loaded nanocochleates (CU-NC) to rats. The chromatographic separation was performed on HIQ SIL, C18 (250 mm × 4.6 mm) column using methanol and water (80:20 v/v) as mobile phase, at 1.0 mL/min flow rate. Validation parameters included linearity, accuracy, precision, and limit of quantitation and detection. Good linearity was obtained over the range of 2.5–100 μg/mL (R2 = 0.9979) of curcumin. The developed HPLC method was precise, with <2% relative standard deviation. Accuracy, stability, and robustness studies were also found to be acceptable. Bland-Altman plot showed an acceptable repeatability coefficient. The method was under statistical control, revealed by a control chart. After CU–NC administration, pharmacokinetic parameters i.e. Cmax, AUC0-∞, and AUMC0-∞, were observed to be 97.69 ± 10.84 μg/mL, 1402.77 ± 9.67 (μg/mL) ∙ h, and 35140.16 ± 14.67 (μg/mL) ∙ h2, respectively. This simple and precise method can be effectively implemented for routine analysis.