N,N-Dimethylformamide (DMF), N-methyl-2-pyrrolidone, and dichloromethane (DCM) are the most widely used solvents for Fmoc solid-phase peptide synthesis (SPPS). These solvents are considered hazardous chemicals and are normally used in large amounts for washing, deprotection, and coupling steps. Therefore, the use of these reagents is indeed in question. Our group recently reported the use of 2-methyltetrahydrofuran (2-MeTHF), which is a green solvent, for coupling, but using DMF for the Fmoc removal and washing steps [Jad et al. Amino Acids 2016 , 48 ( 2), 419−426.]. Herein, total full green solvent protocols in which DMF and DCM are completely eliminated are reported. Several green solvents, such as 2-MeTHF, ethyl acetate, and isopropyl alcohol; temperature; solid supports; and peptide models were evaluated in this study. The best green protocol established is the use of 2-MeTHF for Fmoc removal, washing, and coupling steps with some more washing with EtOAc at room temperature for a short and challenging peptide (Aib-enkephalin pentapeptide). In the case of a longer and more difficult peptide (Aib-ACP decapeptide), the best protocol established was similar, except for the Fmoc removal and coupling steps that were conducted at 40 °C and in combination with the use of a polyethylene glycol resin (ChemMatrix resin).