Various anti-nutritional compounds (including phytic acid, saponin, oxalate, and …) that naturally exist in grains and seeds, playing an essential role in the growth and survival of plants, are considered as limiting factors for human consumption due to their different disadvantages such as disturbance in the function of digestive enzymes or decrease in the bioavailability of various types of ions, minerals, and vitamins and should be reduced or eliminated. However conventional methods (e.g. thermal processing), have low efficiency in reducing the anti-nutritional substances, negatively impact the quality parameters of the foods, are time-consuming, and in some cases require the use of chemicals that limit the commercial usage of conventional methods. Non-thermal processing such as irradiation, cold plasma, high pressure, ultrasound, pulsed light, and pulse electric field, has been given attention recently for reducing the anti-nutritional content of the foods. The effectiveness of these methods depends both on the main factors related to each type of processing method, and on the type and concentration of anti-nutritional substance and the effective method can be identified based on the type of anti-nutritional substance present in different kinds of seeds and grains. Therefore this review is focused on investigating the effectiveness of novel non-thermal processing on the anti-nutritional compounds of seeds and grains.