Motor impairment

This refers a wide range of conditions that make it difficult or impossible to use a mouse or keyboard. People with these conditions may be more easily fatigued by prolonged use. On the face of it there might seem little that can be done to assist here.

Gamepad support

Ren'Py has built-in support for using a gamepad (controller) instead of a keyboard and mouse. If you have one of the game pads Ren'Py knows about then the Help screens will include a "tab" for gamepad and list the controls:

Assistive technologies can be mapped to appear as a gamepad with additional electronics potentially making any game that can be played with a gamepad accessible.
See Hackaday: Adaptive Controllers 

Challenges

Some of the challenges with using a gamepad are:

Gamepad not recognised

On Windows at least Ren'Py's recognition of a specific make of gamepad doesn't actually stop it being used. My very cheap original xbox-like controller does work, but it is not one Ren'Py recognises. I altered the contents of screen help(): in screens.rpy to always show the Gamepad help on Windows as it seemed daft to hide the fact that this is an option. There are fully able-bodied people that prefer to play using a gamepad.

screen help():
    ...
                if GamepadExists() or renpy.windows:
                    # On Windows always show the Gamepad menu as Windows recognises more controllers than RenPy does.
                    textbutton _("Gamepad") action SetScreenVariable("device", "gamepad")

Keyboard input

The need to use the keyboard at all is limited in most visual novels. The most common I've seen is to enter a name for the player character. By simply adding a default if the name input is left blank this is much less of an issue.

Mouse input

Mouse functions can largely be replaced by the gamepad. In situations where the player must point at something make sure the focus order is sensible so stick and d-pad navigation works. Gestures, such as drag and drop, are much harder or impossible with a gamepad, so offer an alternative such as select source, select target.

Fatigue

The nature of a visual novel requires a considerable amount of clicking to progress dialogue and narration. Judicious editing can reduce the amount of clicking to progress through a scene. Providing a shorter version of a scene after it has been seen a few times can also reduce clicking. Being very careful about if and when to use the {w} tag that requires more clicks can also help. This kind of nonsense may be "cute", but I think it has no place in an accessible game:

    pc ".{w}.{w}."
    npc ".{w}.{w}."

Mini-games

Are rarely accessible, especially if they are against the clock. Make such things optional elements of the game.