I don't think you can, aside from just making the speedrunning route for your game as uninteresting as possible. Doing this without harming your game is probably not possible to plan for, except for being a debugging phenom and just not letting any cool sequence break, out of bounds, etc. type stuff get into your game.
To make routing less interesting, you need there to be some obvious optimal strategy for rerunning the game, with no room for improvement. To make executing a run less interesting, you need the game to provide virtually no mechanical challenge. This includes minute details like making sure all of your menus operate slowly while having plenty of input buffering, ensuring that a skilled player cannot navigate the menus faster than an unskilled player.
My best advice is to just not think about speedrunners. Any energy spent on antagonizing them is wasted. Just make your game fun, and don't go out of your way to fuck it up just to spite speedrunners. You're going to wind up harming your game to spite a minority of players you couldn't give a fuck about. Denuvo logic.
>>714119210People speedrun Diablo games. There are video guides out there you can look at that will tell you how to read the tea leaves of the level generation algorithm so that you can tell where you need to go in the randomly generated levels as soon as you set foot into the first room. RNG is simply no match for speedrunner autism.