Drug active substances that can be used in the treatment of humans exposed to neutron radiation leakages in applications such as nuclear power plants, boron neutron treatment units, laboratory and space research, transportation, and storage of used radioactive wastes were analyzed. The neutron radiation shielding parameters of these drugs were determined using a quasi-experimental Monte Carlo simulation technique (GEANT4) and through experimental methods. Some important reduction parameters, including the effective removal cross-sections, mean free path, half-value layer, and the number of particles passing through the active ingredients of the drugs [Spectinomycin dihydrochloride pentahydrate, Chlortetracycline Hydrochloride, Lincomycin Hydrochloride, Acetaminophen, Trimethoprim, Amikacin sulphate salt, Gentamicin sulphate, Cephalexin Monohydrate and Potassium iodide] were calculated. The neutron radiation absorption measurements were experimentally performed using a241Am–Be fast neutron source and BF3 gas as the neutron detector. In addition, it was investigated whether there was any change in the chemical structure of these active substances after exposure to neutron radiation by using Tandem Mass Spectroscopy. Both the theoretical and experimental results were compared with paraffin. DAI3, DAI6, and DAI8 samples were found to have a respectively 32.03%, 32.47%, 32.84% especially high absorption capacity compared to the other active substances. Paraffin, which is the most widely used in neutron shielding, has an absorption rate of 33.32%. According to their absorption rates, it has been determined that these active substances have an absorption value close to paraffin. It has also been founded that there isn’t any change in the chemical structure of drug active substances after exposure to radiation for 20 min. Thus, it is suggested that these drug compounds can be used as an active substance for a drug to be made for protection against neutron radiation.