Some multi-materials produced via SLM and containing 316L steel may exhibit defects and cracks in the interfacial zone. There is a lack of research on 316L/NiTi multi-materials with an interlayer produced via SLM. This study aims to investigate the influence of a high-entropy alloy (HEA)—CoCrFeNiMn interlayer on the defects’ formation, microstructure, phase, and chemical compositions, as well as the hardness of the interfacial zone. It was concluded that using of high-entropy alloy as an interlayer in the production of 316L/HEA/NiTi multi-material via SLM is questionable, since numerous cracks and limited pores occurred in the HEA/NiTi interfacial zone. The interfacial zone has an average size of 100–200 μm. Microstructure studies indicate that island macrosegregation is formed in the interfacial zone. The analysis of phase, chemical composition, and hardness demonstrates that a small amount of FeTi may form in the island macrosegregation. The increase in iron content in this area could be the reason for this. The interfacial zone has a microhardness of about 430 HV, and in the island macrosegregation, the microhardness increases to about 550 HV. Further research could involve an in-depth analysis of the phase and chemical composition, as well as examining other metals and alloys as interlayers.