In Windows, I have my mouse configured for left-handed use (so "left"-button clicking is on the right), but the game is not recognizing this setting, or is overriding it. How can I get the mouse to work left-handed? thx.
What mouse are you using? Most of them allow to map custom functions to their buttons in their control panel. If it offers a general switch of primary and secondary button, don't use this option, but map the mouse buttons explicitly to left-click and right-click, so that the function of the right mouse button is a left-click and vice versa.
Usually custom mouse settings can also be set for specific programs only. Make sure Giana Sisters isn't on that list while set to standard behavior.