Substitution Cipher Python

Original answer below:

Please show us some sample input and output for an example. Based on your code, I can come up with the following – random.shuffle shuffles everything in place and returns None, change your makeKey to:

def makeKey(alphabet):
   alphabet = list(alphabet)
   random.shuffle(alphabet)
   return ''.join(alphabet)

EDIT 2:

For an approach without using dicts in encryption/decryption, see below:

import random

alphabet = 'abcdefghijklmnopqrstuvwxyz.,! ' # Note the space at the end, which I kept missing.
# You could generate the key below using makeKey (i.e. key=makeKey(alphabet))
key = 'nu.t!iyvxqfl,bcjrodhkaew spzgm'
plaintext = "Hey, this is really fun!"
# v! zmhvxdmxdmo!nll mikbg


def makeKey(alphabet):
   alphabet = list(alphabet)
   random.shuffle(alphabet)
   return ''.join(alphabet)

def encrypt(plaintext, key, alphabet):
    keyIndices = [alphabet.index(k.lower()) for k in plaintext]
    return ''.join(key[keyIndex] for keyIndex in keyIndices)

def decrypt(cipher, key, alphabet):
    keyIndices = [key.index(k) for k in cipher]
    return ''.join(alphabet[keyIndex] for keyIndex in keyIndices)

cipher = encrypt(plaintext, key, alphabet)

print(plaintext)
print(cipher)
print(decrypt(cipher, key, alphabet))

Prints:

Hey, this is really fun!
v! zmhvxdmxdmo!nll mikbg
hey, this is really fun!

EDIT:

After some spacing issues and experimentation, I came up with this rather simple solution:

import random

alphabet = 'abcdefghijklmnopqrstuvwxyz.,! '
key = 'nu.t!iyvxqfl,bcjrodhkaew spzgm'
plaintext = "Hey, this is really fun!"


def makeKey(alphabet):
   alphabet = list(alphabet)
   random.shuffle(alphabet)
   return ''.join(alphabet)

def encrypt(plaintext, key, alphabet):
    keyMap = dict(zip(alphabet, key))
    return ''.join(keyMap.get(c.lower(), c) for c in plaintext)

def decrypt(cipher, key, alphabet):
    keyMap = dict(zip(key, alphabet))
    return ''.join(keyMap.get(c.lower(), c) for c in cipher)

cipher = encrypt(plaintext, key, alphabet)

print(plaintext)
print(cipher)
print(decrypt(cipher, key, alphabet))

This prints:

Hey, this is really fun!
v! zmhvxdmxdmo!nll mikbg
hey, this is really fun!