It does make a difference to which leg you lock down.
For instance, in Mastering the Rubber Guard and Mastering the Twister, Eddie does everything on the same side.
eg.
- strong side lockdown is strong side grapevine (when going for truck/twister)
- overhook you don't want in half guard = over hook for cocoon = hand on mat in Rubber guard = arm you sit on in Twister Side Control
If you're learning, especially through instructionals, it does help keeping everything to the same side so it's less confusing, and you can flow between positions
eg. Specifically for Half Guard
* lets say your strong side Lock Down is with your right leg outside and right underhook
* and your strong side Rubber Guard is with your right foot on the hip, left leg curling, right hand grabbing the ankle
- it might not make that much difference going from half guard to closed guard (opponent leaves knee off the ground and you replace full guard), since you can just choose what side to throw up when you break them down and start going for mission control.
- however, if your opponent passes over your leg in Rubber Guard (and you don't have time to hit the Carni), then you'll be stuck on your weak side Lock Down
Same thing goes for lots of other positions. You don't want to sweep a guy from Jiu Claw and end up in Twister Side Control, only to have to transition over to the other side to start setting up the Fishnet/Twister.
(Ideally it would be great to wreck people from any side, but this rarely happens. It helps to have all your things connect. eg even Marcelo mainly attacks the seatbelt one side, has his x guards on one side, butterfly sweeps and guillotines one side)
TL/DR
Kind of.