This network-based pharmacology study intends to uncover the underlying mechanisms of cannabis leading to a therapeutic benefit and the pathogenesis for a wide range of diseases claimed to benefit from or be caused by the use of the cannabis plant. Cannabis contains more than 600 chemical components. Among these components, cannabinoids are well-known to have multifarious pharmacological activities. In this work, twelve cannabinoids were selected as active compounds through text mining and drug-like properties screening and used for initial protein-target prediction. The disease-associated biological functions and pathways were enriched through GO and KEGG databases. Various biological networks [i.e., protein-protein interaction, target-pathway, pathway-disease, and target-(pathway)-target interaction] were constructed, and the functional modules and essential protein targets were elucidated through the topological analyses of the networks. Our study revealed that eighteen proteins (CAT, COMT, CYP17A1, GSTA2, GSTM3, GSTP1, HMOX1, AKT1, CASP9, PLCG1, PRKCA, PRKCB, CYCS, TNF, CNR1, CNR2, CREB1, GRIN2B) are essential targets of eight cannabinoids (CBD, CBDA, Δ9-THC, CBN, CBC, CBGA, CBG, Δ8-THC), which involve in a variety of pathways resulting in beneficial and adverse effects on the human body. The molecular docking simulation confirmed that these eight cannabinoids bind to their corresponding protein targets with high binding affinities. This study generates a verifiable hypothesis of medical benefits and harms of key cannabinoids with a model which consists of multiple components, multiple targets, and multiple pathways, which provides an important foundation for further deployment of preclinical and clinical studies of cannabis.