Abstract <p>An efficient, sensitive, and eco-friendly ultra-high-performance liquid chromatography-tandem mass spectrometry method was developed to determine lanreotide in human plasma. The extraction of lanreotide and lanreotide-d8 from 300 µL human plasma using an Oasis^® HLB 96-well µElution Plate yielded a consistent mean percentage of recoveries of 73.2%. The extracts were analyzed on a Peptide HSS T3 column under gradient-based separation conditions with a flow rate of 0.3 mL/min. The mobile phase consisted of 0.1% formic acid in water and acetonitrile. The detection was performed using a tandem mass spectrometer in positive ionization mode. Multiple reaction monitoring was used to analyze doubly charged precursor ions for lanreotide (<i>m</i>/<i>z</i> 548.8 → 170.0) and lanreotide-d8 (<i>m</i>/<i>z</i> 552.6 → 170.1). The method demonstrated good linearity over a concentration range of 0.1–20 ng/mL with a correlation coefficient greater than 0.997. The intra- and inter-batch precision (coefficient of variation) ranged from 1.5 to 7.4%, and the accuracy was 94.3–103.6%. The lanreotide-d8-normalized matrix factors ranged from 0.976 to 1.021. The analyte demonstrated sufficient stability under different analytical conditions. Further, the greenness of the developed method was assessed by the Analytical Greenness metric tool, Analytical Eco-Scale, and Green Analytical Procedure Index.</p>