The present study aims to increase the efficiency of a resource from waste to health by valorisation of it through cleaner, eco-friendly and less energy-consuming technical processes such as microwave-asissted (MAE) and supercritical fluid (SFE) extractions. On the other hand, optimization of the processes have been applied utilizing multivariate statistic technique such as Response surface Methodology (RSM) in order to consider any possible interaction between variables with less number of experiments as well as to model a response affected by several variables. The outcome of the present study indicates that the optimum conditions for MAE were 275W of microwave power together with 2g mandarin leaf for 45s; regarding SFE, 50 degrees C, 200bar and 0.39mL/min was found as the optimal condition to obtain the maximum yields of each dependent variable such as total phenolic material (TPM) and total flavonoid material (TFM), respectively. Additionally, antioxidant activity values measured by several methods such as cupric ion reducing antioxidant capacity (CUPRAC), 2,2-diphenyl-1-picrylhydrazyl (DPPH) and 2,2-azino-bis-(3-ethylbenzothiazoline-6-sulfonic acid) diammonium salt (ABTS) were correlated positively with both TPM and TFM in the leaf extracts. Furthermore, scanning electron microscope (SEM) images indicated cell wall disruption in all the treatement groups compared to untreated samples.