The lack of suitable medical adsorbents that exhibit a quick response at the time of an overdose is challenging. In this work, we focused on morphine (MORPH) adsorbents that efficiently abate MORPH during the acute overdose and provide, in a controlled, gradual manner, MORPH antagonist─naloxone (NAL) to effectively and safely reverse overdose and its side effects by using, as sorbent, zirconium metal–organic frameworks (MOFs). Three model MOFs, including UiO-66, UiO-67, and NU-1000, were characterized in terms of their ability to adsorb MORPH as well as NAL release in water and a simulated body fluid (SBF). Single MORPH adsorption on NU-1000 was 100% in water and 90 wt % in SBF solution. At the same time, in a single NAL release in SBF from the prepared NAL@UiO-67 composite was equal to 76%. Additionally, in the simultaneous experiment of MORPH adsorption and NAL release, a designed mixture of NU-1000/NAL@UiO-67 has shown maximum adsorption/release values in SBF solution of 89 and 8%, respectively. The in vivo and in vitro experiments confirmed the exceptional effect of prepared materials on the locomotor activity of mice and the low cytotoxicity of MOFs. In vivo fluorescent imaging has confirmed that the nano-MOFs obtained are mostly accumulated in the liver when administered intravenously.