Mephedrone (4-MMC), due to its psychoactive effects similar to amphetamines and cocaine, and much lower price, is currently one of the most abused drugs by adolescents. Due to its commonness and low price, it is one of the stimulants that causes a strong mental and physical addiction, even leading to overdosing or the occurrence of strong withdrawal effects. In this work, we describe comprehensive spectroscopic and biomedical research on zirconium-based metal-organic frameworks (MOFs) for efficient, yet gradual, 4-MMC removal. Several methods including FTIR, μRaman, 1H NMR, UV–Vis, and DFT were used to characterize the 4-MMC adsorption on MOFs. It was found that due to the structural similarities of both 4-MMC and MOF, spectroscopic signals overlap and the use of combined techniques such as DR UV–Vis/dissolution 1H NMR may be required to comprehensively characterize 4-MMC adsorption. According to the 4-MMC adsorption tests, the adsorption efficiency as well as its kinetics strongly depends on the MOF structure parameters. The maximum 4-MMC adsorption from 1000 μM aq. Solutions were achieved by NU-1000 reaching ca. 45 wt% of adsorption. Additionally, by using the modulated synthesis of UiO-6625% HCl with hydrochloric acid, 4-MMC adsorption efficiency increases from 24 wt% to 35 wt%. The in vitro and in vivo experiments have confirmed that the addition of MOF to the 4-MMC solutions decreases the 4-MMC concentration allowing proper Danio rerio embryo development. Furthermore, the in vivo experiments proved that MOFs are potentially safe for model organisms. Additionally, the in vivo experiments have proven the cardioprotective properties of MOFs.