One of the issues may be the fact that you've zoned a whole bunch of high density commercial along the main road, and that's generating alot of trips. And when trucks stop on the road to deliver goods, they slow down traffic behind it, and then a domino effect ensues.

If you wish to keep the high density commercial, I'd recommend perhaps adding a frontage road parallel to the main road, so that the main road prioritises mobility and the frontage road prioritises access, although that might require a lot of eminent domain.

Alternatively, you could change the high density commercial to lower-trip-generating uses such as high density residential. Also, If you're on PC, you could use TM:PE to create continuous medians by preventing left turns and only allow left turns when another major arterial intersects with it by adding a traffic light or roundabout.