In this contribution, a comprehensive study of the redox transformation, electronic structure, stability and photoprotective properties of phytocannabinoids is presented. The non-psychotropic cannabidiol (CBD), cannabigerol (CBG), cannabinol (CBN), cannabichromene (CBC), and psychotropic tetrahydrocannabinol (THC) isomers and iso-THC were included in the study. The results show that under aqueous ambient conditions at pH 7.4, non-psychotropic cannabinoids are slight or moderate electron-donors and they are relatively stable, in the following order: CBD>CBG≥CBN>CBC. In contrast, psychotropic Δ9-THC degrades approximately one order of magnitude faster than CBD. The degradation (oxidation) is associated with the transformation of OH groups and changes in the double-bond system of the investigated molecules. The satisfactory stability of cannabinoids is associated with the fact that their OH groups are fully protonated at pH 7.4 (pKa is ≥ 9). The instability of CBN and CBC was accelerated after exposure to UVA radiation, with CBD (or CBG) being stable for up to 24 h. To support their topical applications, an in vitro dermatological comparative study of cytotoxic, phototoxic and UVA or UVB photoprotective effects using normal human dermal fibroblasts (NHDF) and keratinocytes (HaCaT) was done. NHDF are approx. twice as sensitive to the cannabinoids’ toxicity as HaCaT. Specifically, toxicity IC50 values for CBD after 24 h of incubation are 7.1 and 12.8 μM for NHDF and HaCaT, respectively. None of the studied cannabinoids were phototoxic. Extensive testing has shown that CBD is the most effective protectant against UVA radiation of the studied cannabinoids. For UVB radiation, CBN was the most effective. The results acquired could be used for further redox biology studies on phytocannabinoids and evaluations of their mechanism of action at the molecular level. Furthermore, the UVA and UVB photoprotectivity of phytocannabinoids could also be utilized in the development of new cannabinoid-based topical preparations.