1. To do what is necessary to ward off someone or something or to ensure that something bad does not happen. These trains have multiple fail-safes built into them to safeguard against derailing or losing control. I'm probably paranoid, but I always lock both the front and rear wheels of my bike to safeguard against theft, even if I'm just going into a store for five minutes.

2. To put protections in place to ward off someone or something from someone or something else or to ensure that something bad does not happen to someone or something. In this usage, a noun or pronoun is used between "safeguard" and "against." I know you want to safeguard your kids against any and all pain, but you can't shield them from everything, nor should you. Our security company specializes in safeguarding small businesses against burglars.