You should also be able to use the number keys to make dialogue selections (at least '1' should work when there are no options, just 'continue').
Is the problem with boxes just in the inventory, or when they are in the game world, as well? Do you have any problem selecting a place on the ground to move, or using ladders/stairs/etc?
Do you have mouse gestures enabled, etc? Try pressing the Cmd key on startup, and see if there are any mouse related options (in D:OS EE, at least, there was a 'Precise mouse tracking' options which could fix a couple of issues).
Try lowering the graphics settings and resolution, or switching to Fullscreen or Fake Fullscreen display mode, to see if that will make a difference.
Try doing a clean boot and then test the game. Start/restart your Mac and hold the Shift key down as soon as the progress bar comes up in the startup window, releasing it after the desktop appears. Alternately, from the login window, hold the Shift key when you click the Log In button, and release it when you see the Dock.
If applicable, disable Steam cloud support either globally (in the client click on the Steam menu and select Settings, and then Cloud) or just for this game (in the library right click Divinity: Original Sin 2 and select Properties, then switch to the Updates tab and check the Steam Cloud section).
Next, try browsing to the '~/Documents/Larian Studios' folder and rename the 'Divinity Original Sin 2 Definitive Edition' subfolder. This folder contains the saved games, configuration files and a level cache folder. Deleting or renaming it will get the game to recreate it on startup; playing the game from a different OSX user account would effectively do the same thing. With Steam running and cloud support enabled, the client would just download the cloud copy of your existing profile. After that, start D:OS 2 DE, create a new profile, start a new game and see if you have the same problem. If a new game is ok, exit and then copy a couple saves from the renamed folder into the newly created profile's ../Savegames/Story folder. If that lets you load the saves and select dialogue options, etc, move the rest of the saves over. If that doesn't help, delete the new Documents D:OS 2 folder and rename the original back again.
