Several alkaloids with anticancer activities have been reported among the Crinum species. In this study, an in silico screening of crinine alkaloids was carried out to identify potential Caspase-3 activators and anti-angiogenic compounds. Thirty-one (31) crinine alkaloids were assessed for drug-likeness using the SwissADME online Web server. Nine (9) alkaloids, satisfying Lipinski’s rules for drug-likeness were selected and screened in silico for cytotoxic properties against cancer and normal cell lines using the Cell Line Cytotoxity Predictor (CLC-Pred). The alkaloids possessing drug-like properties and showing good selectivity towards cancer cell lines were evaluated for Caspase-3 activating and anti-angiogenic activities by docking with the Caspase-3 and VEGFR2 proteins, respectively. The binding energy of the compounds was compared with those of the standard drugs. Powelline, augustine, and undulatine possess drug-like properties and demonstrated good selectivity against lung cancer (A549) and oligodendroglioma (Hs683) cell lines. Among these three compounds, powelline had the best potential as a Caspase-3 stimulant and anti-angiogenic agent. Powelline, augustine, and undulatine are potential lead anticancer agents against human lung cancer and oligodendroglioma.