The main aim of this study is to figure out how well cryptand-2.2.1 (C 2.2.1) and cryptand-2.1.1 (C 2.1.1) macrocyclic compounds (MCs) work as novel extractants for scandium (Sc) by using an artificial neural network (ANN) models in MATLAB software. Moreover, C2.2.1 and C2.1.1 have never been evaluated to recover Sc. The independent variables impacting the extraction process (concentration of MC, concentration of Sc, pH, and time), and a nonlinear autoregressive network with exogenous input (NARX) and feed-forward neural network (FFNN) models were used to estimate their optimum values. The greatest obstacle in the selective recovery process of the REEs is the similarity in their physicochemical properties, specifically their ionic radius. The recovery of Sc from the aqueous solution was experimentally evaluated, then the non-linear relationship between those parameters was predictively modeled using (NARX) and (FFNN). To confirm the extraction and stripping efficiency, an atomic absorption spectrophotometer (AAS) was employed. The results of the extraction investigations show that, for the best conditions of 0.008 mol/L MC concentration, 10 min of contact time, pH 2 of the aqueous solution, and 75 mg/L Sc initial concentration, respectively, the C 2.1.1 and C 2.2.1 extractants may reach 99 % of Sc extraction efficiency. Sc was recovered from a multi-element solution of scandium (Sc), yttrium (Y), and lanthanum (La) under these circumstances. Whereas, at a concentration of 0.3 mol/L of hydrochloric acid, the extraction of Sc was 99 %, as opposed to Y 10 % and La 7 %. The Levenberg-Marquardt training algorithm had the best training performance with an mean-squared-error, MSE, of 5.232x10−6 and 6.1387x10−5 for C 2.2.1 and C 2.1.1 respectively. The optimized FFNN architecture of 4-10-1 was constructed for modeling recovery of Sc. The extraction process was well modeled by the FFNN with an R2 of 0.999 for the two MC, indicating that the observed Sc recovery efficiency consistent with the predicted one.