Antinutritional factors are the compounds synthesized naturally in plants and play an important role in determining the use of plants for humans. The antinutrients in plant foods can negatively impact nutrient absorption and reduce their suitability as human food. However, some antinutrients can have positive health effects when present in low amounts. For instance, compounds like tannins, lectins, saponins, amylase inhibitors, phytic acid, and protease inhibitors can decrease nutrient availability and slow down growth. Yet, at lower concentration, these substances can decrease insulin and blood sugar responses to heavy foods, as well as minimize triglyceride and cholesterol levels in the blood. Additionally, phytates, tannins, saponins, protease inhibitors, and oxalates found in certain traditional foods have been linked to a lower risk of cancer. Moreover, a range of indigenous methods and modern technologies are available, which can be used to lower the concentrations of these antinutritional factors. Hence, this chapter offers a comprehensive overview and updated scientific data on the harmful effects and promisive health benefits of key antinutritional factors found in foods from plants. Various traditional processing and indigenous consumption practices are also highlighted for safe use of food plants for humans.