This study aimed to develop optimal microwave assisted extraction conditions for recovery of phenolic compounds and antioxidant properties from the macadamia skin, an abundant waste source from the macadamia industry. Water, a safe, accessible, and inexpensive solvent, was used as the extraction solvent and Response Surface Methodology (RSM) was applied to design and analyse the conditions for microwave-assisted extraction (MAE). The results showed that RSM models were reliable for the prediction of extraction of phenolic compounds and antioxidant properties. Within the tested ranges, MAE radiation time and power, as well as the sample-to-solvent ratio, affected the extraction efficiency of phenolic compounds, flavonoids, proanthocyanidins, and antioxidant properties of the macadamia skin; however, the impact of these variables was varied. The optimal MAE conditions for maximum recovery of TPC, flavonoids, proanthocyanidins and antioxidant properties from the macadamia skin were MAE time of 4.5 min, power of 30% (360 W) and sample-to-water ratio of 5 g/100 mL. Under these conditions, an extract could be prepared with TPC of 45 mg/g, flavonoids of 29 mg RUE/g of dried macadamia skin.