When Should You Make Your Own Weed Killer? Using weed killer should not be the first step you take to protect your lawn and garden. Finally, if you’ve taken preventative measures and you’re still getting invasive weeds, it’s time to break out the weed killer. Caitlin Castelaz4 To use your homemade weed killer, spray on the leaves and stems of your target plant. Finally, it should go without saying, but don’t spray weed killer (or other substances) on someone else’s property without their permission.