Wet coffee processing produces large amounts of liquid effluent, known as coffee processing wastewater (CPW). CPW is considered a pollutant due to its low pH and high concentrations of organic matter, salts, and nutrients. Because of these characteristics, it is essential to treat this effluent before discharging it into the environment. One promising option, which is still little studied or employed, is coagulation-flocculation followed by dissolved air flotation (C/DAF). Coagulation-flocculation is a simple and efficient method, while dissolved air flotation can allow the same volume of pollutants to be removed from the sediment in a shorter period of time. Conventionally, metallic salts are used in coagulation-flocculation; however, these products can be harmful to the environment and to human health. One possible option for study is replacing the metallic salts by natural coagulants, such as the seeds of Moringa oleiferasp. and cladodes of Hylocereus polyrhisussp. (red pitaya). The aim of this research, therefore, was to evaluate C/DAF using the seeds of Moringa oleiferasp. and a cladode from Hylocereus polyrhisussp. in a saline calcium chloride solution in the treatment of CPW, optimizing the doses of coagulants and salt using a central rotational composite design (CCRD). From the results, it was found that using Moringa oleiferasp., about 80% of turbidity were removed, and that using the H. polyrhisussp. cladode, turbidity removal was about 63%. For the water under study the optimal values for dose and salinity using Moringa oleiferasp. are up to 1.2 g·L−1and 2.5 to 4 g·L−1, respectively. When using Hylocereus polyrhisussp., the optimal values for dose and salinity are between 1.1 and 5 g·L−1, and 2.3 and 3.5 g·L−1, respectively. It can be seen that dissolving natural coagulants in saline solution is an interesting alternative in the treatment of CPW, as it allows a reasonably efficient removal of contaminants without employing other products such as metallic salts or alkalizing products.