How do I open the safe at Gio's Apothecary?

Have you found the safe and got rid of its guardian? If not, come back when you have.

You'll need a hint for the safe combination.

Go out and explore the island until you've found it.

Have you visited the Ship Sculpture lately? It's an actual ship now, or the beginnings of one.

Look at the SIGN next to the ship hull.

Specifically at the DRAWING scratched out on the side.

Do you know the combination now?

The Duchess has none. What is it? (Disclaimer: Any resemblance to a real duchess is purely coincidental.)

Heart. So 1 refers to "heart."

2 points to her crown. She has many of those. What are those?

Diamonds. So 2 is "diamond."

3 points to her ...

"Club."

And what does she dig holes with?

That would be her "spade."

Go back to the safe and rotate the dials until you have heart-diamond-club-spade.

Turn the handle to open and get the strange device piece from inside.