A combined bioassay- and molecular networking-guided isolation strategy led to the discovery of twenty-six new terpenoids (1-26) from the soft coral Sclerophytum humesi. Among these, compounds (±)-1 and (±)-2 possess rare 4/7/6-fused tricyclic carbon skeletons, whereas compound (±)-20 features an unprecedented oxatricyclic framewo​rk. Notably, compound 26 represents a rare dimer, the first example of a metabolite formed from two xeniaphyllane-type diterpenoids through a unique 16-peroxyl bridge. Their structures were elucidated through comprehensive spectroscopic analyses, including NMR, HRESIMS, SOR, ECD, and DP4+ probability analysis. A plausible biogenetic pathway, originating from geranylgeranyl pyrophosphate (GGPP) was proposed to rationalize the formation of the unusual carbon skeleton. Compounds 1-17 exhibited selective cytotoxicity against the MIA PaCa-2 cell line, with IC₅₀ values ranging from 1.35 to 26.13 µM and selectivity indices greater than 3. Western blot analysis further revealed that 4 induces intrinsic apoptosis in pancreatic cancer cells via caspase-dependent cleavage of PARP1. In addition, the terpenoids demonstrated significant multitarget inhibitory activity against enzymes α-amylase, α-glucosidase, lipase, acetylcholinesterase, and butyrylcholinesterase with IC₅₀ ranging from 2.85 to 170.0 µM. Enzyme kinetic analyses, molecular docking, and molecular dynamics simulations further elucidated the mechanisms underlying their biological activities.