Abstract Ionizing radiation is used in many fields in energy, medicine, and industrial applications. Those who are in these areas or cancer patients receiving radiotherapy are at risk for acute or long-term exposure to radiation damage due to these ionizing radiations. Non-toxic new agents are needed to protect intact tissue and cells. In this study, we aimed to determine the gamma and neutron radiation attenuation characteristics of seven different natural compounds (quercetin, menadione, naphthol, caffeine, quinine sulphate, cholesterol and riboflavin) to help users in radiation applications. Gamma radiation attenuation parameters such as the mean free path, mass attenuation coefficient, effective atom number, linear attenuation coefficient, and half-value layer were calculated theoretically with WinXCom software for the energy range 0.015–15 MeV. Fast neutron attenuation criteria, such as mean free path, half-value layer, effective removal cross-sections and transmission neutron number, were theoretically determined with Monte Carlo simulation codes (Geant4). Neutron absorption measurement experiments were also applied in addition to the theoretical results. The neutron radiation absorption capacities were determined for samples with an 241Am-Be 4.5 MeV energy neutron source and portatif-type Canberra brand BF3 gas neutron detector. Neutron attenuation parameters were compared with paraffin to determine the absorption capability of the samples. It was found that the dose 1.1094 (μSv/h) from the source was absorbed by the samples to the following extent: 31.76% (Quercetin), 21.85% (Menadione), 28.85% (Naphthol), 22.94% (Caffeine), 12.51% (Quinine sulphate), 40.44% (Cholesterol) and 20.94% (Riboflavin). From the results, it can be clearly seen that all these drug samples had a good neutron radiation attenuation capacity. This revealed that the examined samples had radiation absorption abilities. It was found that the cholesterol sample had an especially excellent absorption power for both neutron and gamma radiation. The samples investigated in this study could be used to develop radiation-protective drugs.