Calendula officinalis L. is a commercially important plant that finds application in the treatment of various diseases in traditional medicine. The total antioxidant capacity, radical scavenging activity, and total phenolic content of marigold extracts were investigated by Folin, CUPRAC, and DPPH assays, respectively. The optimum operating conditions of microwave-assisted extraction (MAE) including temperature, extraction time, solvent-to-solid ratio, and solvent concentration were ascertained by employing response surface methodology (RSM). The solvent (ethanol) concentration was the most significant operating factor among all responses of MAE. At the optimum extraction conditions, the maximum yield of total phenolic content, total antioxidant capacity, and radical scavenging activity obtained experimentally were very close to their predicted values, thus showing the suitability of the model used and the success of RSM in optimizing the extraction conditions. Chromatographic analysis of marigold extract was performed by UPLC-PDA-ESI-MS/MS system and chlorogenic acid was the main component (1742.50 +/- 42.23 mu g/g DS).