A method for manufacturing a shoe sole with multi-material spikes includes: providing a spike-forming mold which includes an upper mold and a lower mold, wherein the lower mold includes a first filling hole which is in communication with the first spike cavity, different materials are placed in the first spike cavity to form the multi-material spike; providing a first mold which includes a second spike cavity; providing a second mold which includes a second filling hole; assembling the first and second molds, together to form a sole cavity, wherein the multi-material spike is placed into the sole cavity, a sole material is filled into the sole cavity through the second filling hole, and then the multi-material spike and the sole material are adhered to each other by hot melting; and opening the first and second molds, and obtaining a shoe sole with the multi-material spike.