Example methods and systems for service request handling with protocol translation are described. In one example, in response to intercepting a service request from a virtualized computing instance, a computer system may generate and send a translated service request towards a service node. The translated service request may be generated by performing a first translation of the service request from a service protocol to a data exchange protocol supported by both a client node running on the computer system and a service node. In response to receiving the service response that is generated according to the data exchange protocol from the service node, the computer system may generate and send a translated service response towards the virtualized computing instance. The translated service response may be generated by performing a second translation of the service response from the data exchange protocol to the service protocol.