Both bio-helical toughening and fiber hybridization provide significant strengthening effects on the penetration properties of composite, and their combination may lead to even greater breakthroughs. Hence, this study explores the synergistic strengthening mechanism of bio-helical unidirectional-basalt fiber composite (BFRP) and weave-carbon fiber composite (CFRP) hybrid composite laminates (HFRP) subjected to penetration load. Three kinds of HFRP are designed and fabricated, and the quasi-static penetration tests and finite element simulations are conducted to evaluate the mechanical properties. Results show that the bio-helical HFRP samples present a significant improvement in anti-penetration property and energy-absorption as compared to other traditional samples. The penetration behaviors of each laminate present a good consistency between experiment and simulation. It is indicated that as the helical angle θ increases, the strengthening effect gradually increases, but when θ continues to increase, it tends to be stable. The penetration failure mechanism and energy-absorbing mechanism are analyzed by experiment and simulation. Finally, it is revealed that bio-helical toughening with hybrid effect from weave-CFRP can form a synergistic strengthening mechanism. This study provides an important reference for the anti-penetration design of aerospace composite with multi-mechanism cooperation.