Nano- and microplastic particles are a global and emerging environmental issue that might pose potential threats to human health. The present work exploits artificial intelligence (AI) to identify nano- and microplastics in water by monitoring the interaction of the sample with a sensitive surface. An estrogen receptor (ER) grafted onto a gold surface, realized on a nonexpensive and easy-to-produce plastic optical fiber (POF) platform in order to excite a surface plasmon resonance (SPR) phenomenon, has been developed in order to carry out a “smart” sensitive interface (ER–SPR–POF interface). The ER–SPR–POF interface offers output data useful for exploiting a machine learning-based approach to achieve nano- and microplastic particle sensors. This work developed a proof-of-concept sensor through a training phase carried out by different particles, in terms of materials and size. The experimental results have demonstrated that the proposed “smart” ER–SPR–POF interface combined with AI can be used to identify the kind of particles in terms of the materials (polystyrene; poly(methyl methacrylate)) and size (20 μm; 100 nm) with an accuracy of 90.3%.