Pineapple (Ananas comosus) peel is a major waste product, derived from pineapple juice processing. It contains a lot of useful bioactive substances like flavonoids, phenolics and enzymes like bromelain. The goal of the current study is to optimize the extraction of these bioactive compounds using various solvent compositions and ultrasound-assisted extraction (UAE) parameters. Under various conditions (40 °C and 60 °C; 20 and 40 min; 1:10 and 1:20 solvent-to-peel ratios), dried and ground pineapple peel was exposed to UAE. With the highest yield of 37.17 mg gallic acid equivalent (GAE) g-1 at 40 °C for 40 min and a 1:20 solvent-to-peel ratio, quantitative analysis indicates that ethanol was the most effective solvent for extracting total phenolic content (TPC) under these conditions. Ethanol also produced the highest total flavonoid content (TFC) [0.049 mg quercetin equivalent (QE) g-1]. On the other hand, at 60 °C for 40 min and a 1:10 solvent ratio, the water/ethanol mixture exhibited the highest antioxidant activity (77.17 %). These results demonstrate the enormous potential of pineapple peel as a source of naturally occurring bioactive compounds. Certain solvents and UAE conditions optimise the extraction of various compounds, providing a sustainable method for waste valorisation in the food and pharmaceutical industries.