In the recent drug analysis arena, optimizing a green, eco-friendly, and cost-effective technique is the main target. In order to cope with green analytical chemistry principles and the trending development of miniaturized portable and handheld devices, an innovative microfabricated ion-selective electrode for the analysis of metoclopramide (MTP) was developed. The fabricated electrode adopted a two-step optimization process. The first step of optimization depended on screening different ionophores in order to enhance the sensor selectivity. Calix-4-arene showed the maximal selectivity towards MTP. The second step was utilizing a graphene nanocomposite as an ion-to-electron transducer layer between the calix-4-arene polymeric membrane and the microfabricated copper solid-contact ion-selective electrode. The graphene nanocomposite layer added more stability to electrode potential drift and short response times (10 s), probably due to the hydrophobic behavior of the graphene nanocomposite, which precludes the formation of a water layer at the Cu electrode/polymeric membrane interface. The proposed MTP sensor has been characterized according to IUPAC recommendations and the linear dynamic range estimated to be 1 × 10-6 to 1 × 10-2 M with LOD of 3 × 10-7 M. The proposed sensor has been successfully employed in the selective determination of MTP in bulk powder, pharmaceutical formulation, and biological fluid. No statistical significant difference was observed upon comparing the results with those of the official method. The Eco-score of the method was assessed using the Eco-Scale tool and was compared with that of the official method. Graphical abstract.