AbstractGhee is a major Indian dairy product with a pleasant flavor. During its manufacture, ghee residue is obtained as the by‐product, which consists of substantial quantity of phospholipids. Phospholipids exhibit emulsifying properties and offer some health benefits. The present study aimed to optimize the process parameters for the extraction of phospholipids from ghee residue (GR) using ultrasonication. The GR was subjected to a series of pre‐treatments before ultrasonication. The hot water treatment led to reduction in nonpolar lipids and improved polar lipids (35.47% fat basis). Taguchi orthogonal array design was employed for optimization of ultrasound power, treatment temperature, time and solvent:solid (S:S) ratio with phospholipid content and antioxidant activity as the response variables. The phospholipid content ranged between 18.54% and 23.89% and antioxidant activity of the extracted samples varied from 47.01% to 50.64% expressed as radical scavenging activity by DPPH assay, while for the untreated GR, the PL and antioxidant activity were 4.98% and 32.75%, respectively. The power level of 80%, 80°C treatment temperature, S:S ratio of 15 and sonication time of 4 min. resulted in maximum extraction of phospholipids (24.12%). The yield of phospholipids was quantified as 13.1% and 8.88% by two elution techniques using solid phase extraction methods. The predicted and experimental values for the responses were in good agreement with R2 value of 0.98. Power and temperature were found to be significant (p < 0.01) in influencing phospholipids yield. For antioxidant activity of the extract, S:S ratio exerted significant effect (p < 0.01). The experimental data were fit in four defined empirical models for understanding the extraction kinetics. Based on the R2 values, the models explained the kinetics in the following order: Parabolic model>Power law>Peleg's model>Elovich's model.Practical applicationsPresently, ghee residue is often discarded as waste or used as animal feed by most of the ghee manufacturing dairy plants. Few studies were conducted to incorporate ghee residue as an ingredient in different food products. However, the present study opens new avenues for utilization of this by‐product for extraction of high value bioactive components, that is, phospholipids, with the help of novel technology; namely ultrasonication. The phospholipids have techno‐functional properties as an emulsifier. One of the classes of phospholipids, that is, sphingomyelin has unique health benefits, therefore this extract will also have scope as a nutraceutical. Thus, there is great practical utility for the present findings. In addition, for the scaling up of extraction techniques, the understanding of mass transfer kinetics is very vital and the same had been studied in the present investigation. Thus, the findings of this study are helpful in determining the ideal ultrasound‐assisted extraction conditions for extraction of phospholipids from ghee residue. Kinetics of extraction will help to explore opportunities for scale‐up of the process.